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PubMed2003

[Vascular access, an underestimated source of inflammation in dialysis patients].

The surveillance of inflammation in dialysis patient, by means of sensitive markers such as CRP, is strongly recommended in a continuous quality improvement treatment approach. Chronic inflammation being deleterious via several pathways including malnutrition, accelerated arteriosclerosis and beta 2M-amyloidosis, microinflammation must diagnosed and corrected as soon as possible in dialysis patients. Vascular access represents an underestimated source of inflammation in hemodialysis patients. In the absence of organic cause of inflammation, the vascular access should be always incriminated and meticulously investigated. Withdrawing the suspected prosthetic or unused material (PTFE or catheter) should be considered as the best way of correcting the inflammation and restoring the recombinant erythropoietin (EPO) activity in the dialysis patient.

Acute Disease↗
PubMed2004

Relationship between bone marrow-derived CD34 + cells expressing interleukin-5 receptor messenger RNA and asthmatic airway inflammation.

BACKGROUND: Asthma is clinically related with the degree of eosinophilic inflammation. How asthmatic airway inflammation is affected is still poorly understood. So the effects of bone marrow-derived hematopoietic cells expressing CD(34) (CD(34)(+)) and interleukin-5 (IL-5) receptor messenger RNA (IL-5R mRNA+) on asthmatic airway inflammation were investigated. METHODS: Balb/c mice were sensitized and challenged by ovalbumin (OVA) to establish an asthmatic model while control mice were sensitized and exposed to sterile saline. The mice were killed at different time points after being challenged by OVA and sterile saline. Then, bronchoalveolar lavage fluid (BALF), peripheral blood (PB) and bone marrow (BM) were prepared. Eosinophils in PB (PBEOS) and BALF (BALFEOS), nuclear cells in BALF, PB and BM were counted. By flow cytometry, the percentage of CD(34)(+) cells to nucleated cells in PB, BM and the relative number of CD(34)(+) cells in PB (PBCD(34)(+)) and BM (BMCD(34)(+)) were calculated. Immunocytochemistry and in situ hybridization were used to investigate the hematopoietic cells with co-localized expression of CD(34) and IL-5R mRNA in BM (BMCD34+IL-5R mRNA+). The percentage of BMCD34+IL-5R mRNA+ to BMCD(34)(+) was calculated. RESULTS: Twelve hours after challenge by OVA, BALFEOS and PBEOS in the experimental group were significantly higher than those in the control group (P < 0.01). Twenty-four hours after OVA challenge, BALFEOS, PBEOS and BMCD34+IL-5R mRNA+ were elevated maximally, significantly different from those in the control group (P < 0.01). Forty-eight hours after OVA challenge, BALFEOS and BMCD34+IL-5R mRNA+ were still significantly higher than those of the controls (P < 0.01). The other markers reverted to normal. In 60 mice, BMCD34+IL-5R mRNA+ was closely correlated with the BALEOS, PBEOS, BMCD(34)(+) and BMCD(34)(+) (%) (P < 0.05). CONCLUSIONS: The amount of CD(34)(+) cells expressing IL-5R mRNA increased in the BM of asthmatic model mice, which favors eosinophilopoiesis and eosinophilic airway inflammation. A signal pathway exists between the lungs and the bone marrow, which is involved in the initiation and maintenance of asthmatic airway inflammation.

Animals↗
PubMedDate not supplied

[The role of neuromodulators (substance P and calcitonin gene-related peptide) in the development of neurogenic inflammation in the oral mucosa].

Vatous observations carried out in the course of the years have shown that certain neuropeptides have a possible role to play as inflammation mediators. The substances on which attention has been principally focused are: substance P, calcitonin gene-related peptide, capsaicin an histamine. Knowledge acquired in this field, however, does not yet permit us to sufficiently clarify the role, not to speak of the possible action mechanism, on the basis of which these neuropeptides act, although it is confirmed that these substances have been found first in laboratory animals and later also in human tissues in the course of experimentally induced neurogenic inflammation. The need to know more and more about inflammatory mechanisms and the increasingly complex possibilities offered by the application of technology in the field of medical research have led to many small advance in our knowledge of what is involved in inflammation. In fact it has been understood that behind the typical signs of inflammation (the famous four cardinal signs of Celsus: pain, redness, swelling, heat) no abstract entities or strange alchemies are concealed, but a series of well-known, classified substance, the so-called "inflammation mediators", namely a variety of substances of cellular or plasmatic origin united by the fact that exist, in stationary state conditions, in the form of inactive precursors, or sequestered in intracellular sites where they are unable to carry out their action. Following an inflammatory stimulus, they are activated, or their synthesis can be induced, or their release from intracellular sequestration sites in favoured; in any case they are stored in the disturbance district in concentrations that are such as to act on their respective targets, triggering event s that characterise the various stages of the inflammatory process.

Calcitonin Gene-Related Peptide↗
PubMed2004

International symposium on nitric oxide, cytokines and inflammation.

This meeting was presented by the Fundacao Oswaldo Cruz in conjunction with the University of Calgary and the University of California Los Angeles. The conference focused on novel aspects of the contribution of nitric oxide and cytokines to inflammatory processes, particularly the resolution of inflammation. Sessions featured lectures and symposia by many of the world's leading authorities on the basic science and pharmacology of inflammation, as well as lively, high-standard poster presentations by international scientists, including many young Brazilian researchers. One of the main topics was elucidation of the basic mechanisms and roles of cytokines in inflammation. Moreover, the therapeutic potential of new chemical entities (some derived from snake venoms) and drug targets was highlighted in symposia devoted to the resolution of inflammation, airway inflammation, protease-activated receptors and annexin-1. This report concentrates on potential novel therapeutic agents and targets in this complex and ever-evolving field, although many interesting presentations raised the possibility of new applications for drugs already in the therapeutic arena.

Animals↗
PubMed2004

Systemic inflammation in dialysis patients with end-stage renal disease: causes and consequences.

Despite rapid improvements in dialysis technology during the last 20 years, the mortality rate in end-stage renal disease (ESRD) patients treated with dialysis is still unacceptably high and comparable to that of many cancer patients with metastases. The main cause of the increased mortality in ESRD patients is cardiovascular disease (CVD), which is twice as common and advances at twice the rate already in patients with earlier stages of chronic kidney disease as compared to the general population. Although traditional risk factors are common in dialysis patients, they can only in part explain the very high prevalence of CVD in this patient group. Recent evidence demonstrates that chronic inflammation, a non-traditional risk factor which is a commonly observed in dialysis patients, may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. Available data suggest that pro-inflammatory cytokines play a central role in the genesis of both malnutrition and CVD in ESRD. While the long-term effects of chronic inflammation may be most important in the pathogenesis of CVD, the acute-phase reaction may also be a direct cause of acute vascular injury by several pathogenetic mechanisms. The cause(s) of inflammation in dialysis are multifactorial and include both dialysis-related and unrelated factors. Thus, it could be speculated that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) would improve survival in dialysis patients. As there are currently no established guidelines for the treatment of chronic inflammation in ESRD patients, studies on the long-term effects of various anti-inflammatory treatment strategies on the nutritional and cardiovascular status as well as outcome in this patient group are warranted.

Humans↗
PubMedDate not supplied

Hematopoietic secretory granules as vehicles for the local delivery of cytokines and soluble cytokine receptors at sites of inflammation.

Cytokines play an important role in the regulation of homeostasis and inflammation. A de-regulated cytokine function can subsequently promote chronic inflammation. This is supported by clinical evidence showing the beneficial effect of inhibiting TNF-alpha through injection of antibodies and soluble receptor in disorders such as rheumatoid arthritis and Crohn's disease. Systemic anti-TNF-alpha therapy however is associated with infectious complications. We therefore suggest a concept for the local deposition of therapeutically active agents into areas of inflammation or malignancy, based on the use of hematopoietic storage and secretory granules as delivery vehicles. Hematopoietic cells are induced to express the therapeutically active protein and to store it in the secretory lysosomes. The cells migrate into a tumour or site of inflammation, where the cells become activated and release the contents of their secretory lysosomes resulting in the local delivery of the therapeutically active protein. In support of this concept, gene transfer and granule loading can be achieved using the soluble TNF-alpha receptor (sTNFR1) after cDNA expression in hematopoietic cell lines. Endoplasmic reticulum (ER)-export can be facilitated by the addition of a transmembrane domain, and constitutive secretion can be prevented by incorporating a cytosol-sorting signal resulting in secretory lysosome targeting. The sTNFR1 is released from the transmembrane domain by proteolytic cleavage and finally, regulated sTNFR1-secretion can be triggered by a calcium signal. In vivo investigations are currently determining the feasibility of local protein delivery at sites of inflammation.

Animals↗
PubMed2005

Correlations between edema and the immediate and prolonged painful consequences of inflammation: therapeutic implications?

The precise relationship between the degree of pain and the degree of inflammation in the individual remains debated. A quantitative analysis simultaneously applied to the immediate and prolonged painful consequences of inflammation has not yet been done. Thus, the correlations between edema, nociception and hypersensitivity following an inflammatory insult were assessed in rodents. To better understand the therapeutic value of modifying specific aspects of inflammation, the effects of an anti-inflammatory drug were compared to the results. Inbred strains of mice and outbred rats received an intraplantar injection of honeybee venom and the between-group and within-group correlations were calculated for spontaneous nociceptive measures, thermal and mechanical hypersensitivity, and edema and temperature. The effect of indomethacin on the pain and inflammation measures was examined. Edema correlated with spontaneous flinching, licking and lifting of the injected paw (P< or =0.003), and not with thermal or mechanical hypersensitivity. Indomethacin affected edema and spontaneous nociception dose-dependently, and affected hypersensitivity only at the highest dose tested (P< 0.05). These results suggest that edema may contribute only to immediate spontaneous nociceptive responses to an inflammatory insult, and not to the more clinically relevant prolonged hypersensitivity. This analysis represents a method for determining which inflammatory processes are the most promising therapeutic targets against the multiple painful consequences of inflammation.

Animals↗
PubMed2005

[The effect of gamma interferon gene transfer on airway inflammation in asthmatic mice].

OBJECTIVE: To study the effect of airway gamma interferon (IFN-gamma) plasmid gene transfer on airway inflammation in asthmatic mice. METHODS: Forty C57BL/6 mice were randomly divided into four groups: a control group (group A), an asthmatic group (group B), a plasmid group (group C) and an IFN-gamma plasmid group (group D), 10 mice in each group. Except group A, other groups were sensitized with 0.1 ml 0.1% ovalbumin (OVA) by a combination of intraperitoneal injection and repeated 50 microl 1% OVA intranasal challenges to establish the mouse asthma model. In group A, normal saline of the equal volume was given instead of 0.1% OVA 0.1 ml and 1% OVA 50 microl. Group C was intranasally administered 50 microl mixture of plasmid pcDNA3.1(-) and Lipofectamine 2000, while 50 microl mixture of IFN-gamma plasmid and Lipofectamine 2000 was administered for the mice of group D. Bronchoalveolar lavage fluid (BALF) cell count and differential were studied. Interleukin-4 (IL-4), interleukin-5 (IL-5) and IFN-gamma in BALF were determined. Pathologic changes in lung tissues were observed. RESULTS: The differences were significant (P < 0.05) when the numbers of inflammation cells, eosinophils, neutrophils and lymphocytes in BALF of group B [(0.102 +/- 0.020) x 10(9)/L, (0.0193 +/- 0.0047) x 10(9)/L, (0.0107 +/- 0.0039) x 10(9)/L, (0.0255 +/- 0.0042) x 10(9)/L, respectively] were compared with those of group A [(0.082 +/- 0.012) x 10(9)/L, (0.0041 +/- 0.0009) x 10(9)/L, (0.0051 +/- 0.0016) x 10(9)/L, (0.0201 +/- 0.0019) x 10(9)/L, respectively]. The numbers of inflammation cells, eosinophils, neutrophils and lymphocytes in BALF of group D [(0.086 +/- 0.016) x 10(9)/L, (0.0116 +/- 0.0031) x 10(9)/L, (0.0062 +/- 0.0018) x 10(9)/L, (0.0182 +/- 0.0041) x 10(9)/L, respectively] were also significantly different (P < 0.05) as compared with those of group B. The IL-4, IL-5 and IFN-gamma levels in BALF of group B [(39.2 +/- 5.1) pg/ml, (83.7 +/- 4.7) pg/ml, (15.7 +/- 2.7) pg/ml, respectively] were significantly different (P < 0.05) as compared with those of group A [(13.3 +/- 1.9) pg/ml, (12.1 +/- 2.3) pg/ml, (31.8 +/- 7.9) pg/ml, respectively]. The IL-4, IL-5 and IFN-gamma levels of group D [(16.4 +/- 3.2) pg/ml, (26.3 +/- 3.4) pg/ml, (65.4 +/- 10.4) pg/ml] were also different (P < 0.05) from those of group B. Lung inflammation was examined in HE stained sections. There was no obvious infiltration of inflammatory cells in the airways of group A. However, there were a great number of inflammatory cells in the interstitial and peribronchovascular regions of group B and group C. Group D exhibited reduced epithelial damage and less infiltration of mononuclear cells and polymorphs in the interstitial and peribronchovascular regions, as compared with group B or group C. CONCLUSIONS: These findings suggest that transtracheal IFN-gamma gene transfer is effective in modulating the imbalance of Th1/Th2 in BALF and inhibiting airway inflammation of asthmatic mice. The result provides experimental data for developing a novel therapeutic approach to asthma.

Animals↗
PubMedDate not supplied

Can the inflammation markers of patients with high peritoneal permeability on continuous ambulatory peritoneal dialysis be reduced on nocturnal intermittent peritoneal dialysis?

BACKGROUND: Patients with high peritoneal permeability have the greatest degree of inflammation on continuous ambulatory peritoneal dialysis (CAPD), which may be associated with their higher mortality. Nocturnal intermittent peritoneal dialysis (NIPD; "dry day") may decrease inflammation by reducing the contact between dialysate and peritoneum and/or providing better fluid overload control. Therefore, the aims of this study were to determine and compare serum and dialysate concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) of patients with high or high-average peritoneal transport on CAPD, changed to NIPD, and ultimately to continuous cyclic peritoneal dialysis (CCPD). METHODS: Crossover clinical trial in 11 randomly selected patients. All subjects had been on CAPD and were changed to NIPD, and ultimately to CCPD (6.4 +/- 3.1 months after initiation of study). All patients used glucose-based dialysate. Evaluations of clinical and biochemical parameters, dialysis adequacy, and serum and dialysis inflammation markers were performed at baseline on CAPD, 7 - 14 days after changing to NIPD, 7 - 14 days after switching to CCPD, and after 1 year of follow-up. All patients used only 1.5% glucose dialysate during evaluation days. CRP was determined by nephelometry, and IL-6 and TNF-alpha by ELISA. RESULTS: Seven patients were high transporters and 4 high average. Ultrafiltration increased (p < 0.05) when patients changed from CAPD [0.38 L (-0.3 - 1.1 L)] to NIPD [2.64 L (0.7 - 4.7 L)]; it then decreased on CCPD [0.88 L (0.4 - 1.3 L) and at the end of study [0.65 L (0.3 - 1.0 L)]. This better fluid overload control was accompanied by decreased weight and systolic and diastolic blood pressure when patients changed from CAPD (89 +/- 13 kg, 160 +/- 23 and 97 +/-9 mmHg, respectively) to NIPD (86 +/- 17 kg, 145 +/- 14 and 86 +/- 9 mmHg, respectively), and increased weight and systolic and diastolic blood pressure on CCPD (85 +/- 15 kg, 143 +/-23 and 88 +/- 14 mmHg, respectively) and at the end of follow-up (87 +/- 16 kg, 155 +/- 24 and 89 +/- 12 mmHg, respectively). Median serum CRP decreased (p = 0.03), from 3.8 (1.6 - 8.5) mg/L on CAPD to 1.0 (0.4 - 4.4) mg/L on NIPD, but increased on CCPD [1.8 (1.3 - 21) mg/L] and at the end of the study [3.2 (0.3 - 8.2) mg/L]. Dialysate CRP decreased nonsignificantly, from 0.10 (0 - 0.5) mg/L on CAPD to 0 (0 - 0.03) mg/L on NIPD, to 0.01 (0 - 0.08) mg/L on CCPD, and to 0 (0 - 0) mg/L at final evaluation. Serum TNF-alpha concentration decreased, from 0.14 (0.04 - 0.6) pg/mL on CAPD to 0.01 (0 - 0.08) pg/mL on NIPD, and then increased to 0.06 (0 - 0.4) pg/mL on CCPD and to 0.11 (0 - 0.2) pg/mL at the end of the study; whereas dialysate TNF-alpha decreased, from 0.08 (0.03 - 0.2) pg/mL on CAPD to 0.04 (0 - 0.2) pg/mL on NIPD, and to 0 (0 - 0) pg/mL and 0 (0 - 0.05) pg/mL on CCPD and final evaluation respectively. Serum IL-6 decreased (p = 0.07), from 2.5 (2.0 - 4.2) pg/mL on CAPD to 1.0 (0.7 - 2.0) pg/mL on NIPD, and to 1.0 (0.8 - 2.9) pg/mL on CCPD and 1.0 (0.5 - 9.8) pg/mL at the end of the study; whereas dialysate levels remained similar on CAPD [8.0 (3.7 - 13) pg/mL] and NIPD [7.8 (5.1 - 23) pg/mL], and increased on CCPD [11.2 (9.5 - 19) pg/mL] and at final evaluation [11.2 (8.3 - 15) pg/mL]. CONCLUSIONS: NIPD significantly decreased serum CRP and displayed a trend to decrease TNF-alpha and IL-6 serum concentrations compared with CAPD; whereas CCPD tended to reverse these effects. These results did not appear to be due to decreased local peritoneal inflammation, but they could be associated with better control of fluid overload on NIPD. Thus, NIPD, as Long as the residual renal function allows it, may be useful in reducing the systemic inflammation of patients with high peritoneal membrane permeability.

Adult↗
PubMedDate not supplied

The contribution of Rudolf Virchow to the concept of inflammation: what is still of importance?

At the beginning of the 19th century, medicine was based largely on speculative and philosophical concepts. The greatest merit of Rudolf Virchow was without doubt a way of thinking based on natural science. In place of the empirical chaos represented by the doctrines of humors and crasis, he created the new paradigm of cellular pathology. In the field of inflammation, he critically analyzed the meaning of the four key symptoms of inflammation (redness, swelling, heat and pain) and postulated that inflammation cannot be represented as a single process but rather constitutes various inflammatory processes. In addition he introduced the functio laesa , denoting the restricted function of inflamed tissues. In the pathogenesis of inflammation, Virchow highlighted the importance of the inflammatory stimulus. The irritatio is the starting point and the conditio sine qua non . Through his pathohistological investigations in experimental animals and in humans, inflammation was widely accepted as the central cause of atherosclerosis, until the end of the 19th century, and has been confirmed in recent decades. It was Virchow who first coined the term endarteriitis deformans . Likewise, he was also the first to hypothesize a link between microinflammation and subsequent cancer development. This hypothesis has recently been corroborated by numerous studies and may have therapeutic consequences. Virchow contributed to nearly all aspects of human pathology and championed the cause of social medicine.

Atherosclerosis↗
PubMedDate not supplied

[The role of macroglobulin family proteins in the regulation of inflammation].

The macroglobulin family represents a group of universal regulators involved into control of the inflammatory response to external and internal pathogens. Alpha-2-macroglobulin (MG), the major protein in the family, has 3 different binding sites and high affinity to an endocytosis receptor that allows MG to participate in recognition and phagocytosis of the foreign agents. The macroglobulin family proteins are most powerful apoptosis inhibitors: they bind autoaggressive hydrolases accumulating during inflammation. MG is the main transporter of cytokines and growth factors controlling the inflammatory response. At the same time, the macroglobulins are negative reactants of an acute phase of inflammation and the decrease of their synthesis at later stages is necessary for stimulation of collagenosis processes, coagulation, activation of thymulin, stimulating NK. At septic inflammation binding of macroglobulins to exotoxins can localize inflammation, and initiate systemic inflammatory response. Macroglobulin damage sharply reduces their subsequent utilization; this provokes accumulation of makroglodulin-proteinase complexes in biological fluids and may cause immune inflammation.

Apoptosis↗
PubMed1990

[Inflammation and rejection].

The inflammation represents an important cause of allograft tissue lesions during ongoing rejection episodes. Such inflammation is mediated, at least in part, via the release of different soluble mediators. Some of these endogenous inflammation mediators are well known and include prostaglandins, leukotriens, histamine or histaminergic compounds and factors induced by the activation of the complement cascade (C3a, C5a). More recently, different molecules have been characterized, namely cytokines that are potent mediators of both immune and inflammatory reactions. Cytokines are produced by a wide variety of cells types (i.e., inducing immune and non immune cells) and expressing pleiotropic effects. The synergism between these various inflammation mediators finally provoke the anatomopathological lesions characteristic of a rejection process that are vascular lesions, edema formation and white blood cell chemotaxis leading to massive cellular infiltration. The aim of this brief review is to analyze the more recent data of the literature concerning cytokines that, applied to the field of organ transplantation, may provide further insights onto the relationships existing between inflammation and allograft rejection.

Cytokines↗
PubMedDate not supplied

Effect of intraarticular tramadol administration in the rat model of knee joint inflammation.

Local administration of exogenous opioids may cause effective analgesia without adverse symptoms from the central nervous system. Experiments show that peripheral antinociceptive effect of opioids is observed especially in inflammatory pain. The aim of the research was to estimate the effect of tramadol on nociceptive process at the level of peripheral nervous system, after its local administration in the model of knee joint inflammation. Tramadol was administered intraarticulary into the rat knee joint, before the inflammation as a preemptive analgesia and, for comparison, after the intraarticular injection of carrageenan. The research determined the influence of tramadol injection on pain threshold for thermal stimuli, development of inflammatory processes using the measurement of joint edema and motor function following the induction of knee joint inflammation in the rat. Functional assessment of knee joint with inflammation, in terms of rats' mobility and body position as well as joint loading and mobility were studied. The results of the experiments show that local administration of tramadol induces antinociceptive effect. The effect of tramadol, which elicits also a decrease in inflammatory edema, appears not only after its administration after carrageenan when inflammation was already present, but also in the case of its injection prior to carrageenan in the scheme of preemptive analgesia. The results of the described research show that not only morphine but also another opioid, tramadol, widely used in clinical practice, inhibits nociception, edema and functional impairment of the paw after its local application directly to the inflamed knee joint.

Animals↗
PubMed2006

CD69 expression on airway eosinophils and airway inflammation in a murine model of asthma.

BACKGROUND: Asthma is a chronic airway disease with inflammation characterized by physiological changes (airway hyper-responsiveness, AHR) and pathological changes (inflammatory cells infiltration and mucus production). Eosinophils play a key role in the allergic inflammation. But the causative relationship between eosinophils and airway inflammation is hard to prove. One of the reasons is lack of activation marker of murine eosinophils. We investigated the expression of CD69 on murine eosinophils in vitro, the relationship between the expression of CD69 on eosinophils from peripheral blood and bronchoalveolar lavage fluid and on airway inflammation in asthmatic mice. METHODS: Eosinophils from peripheral blood of IL-5 transgenic mice (NJ.1638) were purified. Mice were divided into five groups: wild type mice sensitized and challenged with saline (WS group), wild type mice sensitized and challenged with ovalbumin (WO group), IL-5(-/-) mice sensitized and challenged with saline and transferred with purified eosinophils (ISE group), IL-5(-/-) mice sensitized and challenged with OVA and transferred with purified eosinophils (IOE group), IL-5(-/-) mice sensitized and challenged with OVA and transferred with purified eosinophils, pretreated with anti CD4 monoclonal antibody (IOE+antiCD4mAb group). IL-5(-/-) mice were sensitized with OVA at day 0 and day 14, then challenged with OVA aerosol. On days 24, 25, 26 and 27 purified eosinophils were transferred intratracheally to IL-5(-/-) mice. On day 28, blood and BALF were collected and CD69 expression on eosinophils measured by flowcytometry. RESULTS: Purified eosinophils did not express CD69. But eosinophils cultured with PMA + MA, IFN-gamma, IL-5 or GM-CSF expressed CD69 strongly. Eosinophils from blood of WO, WS group did not express CD69 at all. The numbers of eosinophils in BALF of WO group, IOE group, ISE group and IOE + antiCD4mAb group were significantly higher than in mice of WS group which did not have eosinophils at all. CD69 expression on eosinophils in BALF of IOE and WO groups was strong. Eosinophils in BALF of ISE and IOE + antiCDmAb groups did not express CD69. The mucus production result was similar to CD69 expression. There were eosinophils infiltration in lung slides of all groups except WS group. CONCLUSION: Activation in airway of eosinophils could directly lead to airway inflammation.

Animals↗
PubMed1991

Ocular inflammation stimulated by intravitreal interleukin-8 and interleukin-1.

Interleukin-8 (IL-8), a cytokine with neutrophil chemotactic and activating properties, is known to be stimulated by IL-1. Fischer rats are more resistant to inflammation than Lewis rats probably due to a higher corticosteroid stress response. To determine the role of IL-8 in ocular inflammation, the effect of intravitreal injection of IL-8 was compared with that of IL-1 in both Lewis and Fischer rats. The IL-8, IL-1 alpha, or sterile balanced salt solution (control) was injected into one eye of each animal. Both IL-8 and IL-1 alpha caused inflammation in the eye of both strains, as detected by leukocyte counts of the anterior chamber and histopathologic examination. The eyes of animals injected with a cytokine had significantly higher numbers of leukocytes compared with eyes of control animals. Histopathologic examination confirmed these findings. The IL-1 alpha induced inflammation more consistently and more severely than the most effective dose of IL-8. This finding agreed with the concept of IL-1 initiating a cascade of inflammatory mediators including IL-8, which acts more specifically on a smaller population of leukocytes. A contralateral response was observed in the uninjected eye of experimental and control animals. The contralateral response in animals receiving the cytokines was significantly greater than that in controls. Lewis rats show a higher inflammatory response to the injections than do the Fischer rats. These data suggest that IL-8 may be active as one component in neutrophil-mediated ocular inflammation.

Animals↗
PubMed1986

Mediators of airway inflammation.

Mediators of inflammation can be classified into those that exist preformed in cells and those that are rapidly generated following stimulation. Vasoactive amines, lysosomal enzymes, neuropeptides and proteoglycans are examples of classes of mediators that are synthesized and stored, awaiting the proper stimulus that results in their release. Prostaglandins, leukotrienes, platelet activating factors and free radicals are representative substances that are generated as a result of cell activation. It is now clear that similar inflammatory mediators can be produced by diverse cell types. The exact role of specific mediators of inflammation depends on several factors: the precise stimulus that results in their release or production, the time in the overall inflammatory process when they are produced, and their specific biological effects. Upon stimulation, resident cells such as epithelial cells, mast cells and macrophages are in a position to induce inflammation, whereas cells entering sites of initial injury are able to perpetuate the process. Specificity further depends upon cell surface receptors and the mediators resulting from receptor perturbation. Finally, the most critical question is how inflammation, once induced, is limited by the mammalian system in order to prevent this process from unlimited extension. It would appear that numerous mechanisms which limit injury are brought into play with the induction of inflammation. These mechanisms include degradation of mediators by other mediators, mediator degradation by resident cells, and mediator dilution by tissue fluids. In summary, the role of mediators is extremely complex, involving their innate properties, temporal expression, and inactivation.

Arachidonic Acids↗
PubMed1989

The role of arachidonate metabolites in ocular inflammation.

PGs and leukotrienes are said to be mediators of various aspects of inflammation. In the rabbit eye, PGs are primarily involved in vasodilation and at least in rabbits, disruption of the blood-aqueous barrier. These effects vary qualitatively in different species. In the responses of the eye to chemical, mechanical, or neurogenic injury, PG involvement is limited, as indicated by the fact that cyclooxygenase inhibitors do not totally abrogate the responses. Inflammation, whether in the eye or in other tissues, is more complex than the injury responses. Complement pathway, arachidonate metabolites, cytokines, and monokines are major components in inflammation, but not necessarily in the response of tissues to injury. Topical or intracameral administration of leukotriene B4 causes PMN chemotaxis without affecting the blood-aqueous barrier. Peptidoleukotrienes such as leukotriene C4 and D4, on the other hand, are not chemotactic, but they do increase the permeability of the conjunctival microvasculature. Cyclooxygenase and 5-lipoxygenase products have been detected in the anterior chamber during the course of experimentally induced ocular inflammation and in humans with uveitis, but whether their presence is incidental or causal is yet to be established. In spite of numerous investigations, the precise role and the extent of involvement of arachidonic acid metabolites in ocular and non-ocular inflammatory diseases remain controversial. Pharmacologic studies on the effects of CO inhibitors like indomethacin in experimental models of inflammation have provided evidence that PGs participate in vascular reactions but not in leukocyte infiltration. PGs are also capable of interacting with other vasoactive agents to enhance the responses. In humans, such roles for PGs in inflammatory diseases are probably incidental. In patients with rheumatoid arthritis, treatment with CO inhibitors provides symptomatic relief without attacking the underlying cause of the disease. Post-operative vascular leakage is reportedly inhibited by some cyclooxygenase inhibitors (Mishima et al., 1989), but it remains to be seen whether they effectively arrest the processes that in some cases lead to the progression of the disease. Most of the 5-lipoxygenase inhibitors examined to date in experimental animals have been found to be non-selective. Only recently have highly selective 5-LO inhibitors become available, and these are currently being examined. Thus, evidence from animal studies with 5-LO inhibitors suggests the involvement of LTB4 in leukocyte infiltration and of peptidoleukotrienes in bronchospasm as well as in increased microvascular permeability of the conjunctiva and other

Animals↗
PubMed1988

Essential fatty acid deficiency inhibits the in vivo generation of leukotriene B4 and suppresses levels of resident and elicited leukocytes in acute inflammation.

Essential fatty acid (EFA) deficiency exerts an anti-inflammatory effect in several models of inflammation. In an effort to understand underlying mechanisms, the effect of EFA deficiency on the generation of eicosanoids and the elicitation of leukocytes in a model of acute inflammation was examined. Acute inflammation was induced by the i.p. injection of zymosan in mice. The injection of zymosan in normal mice was followed by a short burst of eicosanoid synthesis lasting 2 hr. Leukotriene (LT)B4, LTC4, LTD4, and LTE4, thromboxane B2, and 6-keto-prostaglandin F1 alpha were detected using high pressure liquid chromatography and specific radioimmunoassays. This initial phase of eicosanoid production was followed by a more prolonged infiltration of leukocytes (predominantly polymorphonuclear neutrophils (PMN)) lasting 48 hr with little eicosanoid synthesis. When challenged with zymosan, EFA-deficient mice exhibited a marked decrease in the production of eicosanoids during the early phase. No LTB could be detected at all. The number of resident peritoneal macrophages in EFA-deficient mice was also substantially decreased, and the influx of PMN during the inflammatory response was markedly diminished. In order to establish that the generation of eicosanoids during the early phase of this model of acute inflammation played a causal role in the later infiltration of PMN, the effect of the mixed lipoxygenase/cyclooxygenase inhibitor, BW755C, on LTB formation and PMN influx in this model of inflammation was assessed in control animals. BW755C completely blocked LTB synthesis and inhibited the subsequent influx of PMN. In conclusion, EFA deficiency inhibits eicosanoid generation, depresses levels of resident macrophages, and markedly diminishes the influx of PMN in the acute inflammatory response. The decrease in PMN influx appears to result from the inhibition of the antecedent generation of LTB.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗