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PubMed2004

E-prostanoid-3 receptors mediate the proinflammatory actions of prostaglandin E2 in acute cutaneous inflammation.

PGs are derived from arachidonic acid by PG-endoperoxide synthase (PTGS)-1 and PTGS2. Although enhanced levels of PGs are present during acute and chronic inflammation, a functional role for prostanoids in inflammation has not been clearly defined. Using a series of genetically engineered mice, we find that PTGS1 has the capacity to induce acute inflammation, but PTGS2 has negligible effects on the initiation of this response. Furthermore, we show that the contribution of PTGS1 is mediated by PGE(2) acting through the E-prostanoid (EP)3 receptor. Moreover, in the absence of EP3 receptors, inflammation is markedly attenuated, and the addition of nonsteroidal anti-inflammatory agents does not further impair the response. These studies demonstrate that PGE(2) promotes acute inflammation by activating EP3 receptors and suggest that EP3 receptors may be useful targets for anti-inflammatory therapy.

Animals↗
PubMed2005

Gamma delta T cells regulate the extent and duration of inflammation in the central nervous system by a Fas ligand-dependent mechanism.

Gamma delta T cells have been shown to regulate immune responses associated with inflammation, but the mechanism of this regulation is largely unknown. Using the experimental autoimmune encephalomyelitis (EAE) model of the human CNS autoimmune disease multiple sclerosis, we demonstrate that gamma delta T cells are important regulators of CNS inflammation. This was shown using gamma delta T cell-deficient mice that were unable to recover from EAE. The chronic disease was accompanied by a prolonged presence of both macrophages and lymphocytes in the CNS. This extended inflammatory response was due to alterations in both cell proliferation and death. In mice lacking gamma delta T cells, proliferation of encephalitogenic T cells was 3-fold higher, and caspase activity, indicating apoptosis, was 2-fold lower compared with those in control mice recovering from EAE. gamma delta T cell-deficient mice reconstituted with wild-type gamma delta T cells recovered from EAE and resolved inflammation in the CNS, whereas mice reconstituted with Fas ligand-dysfunctional gamma delta T cells did not. Thus, gamma delta T cells regulate both inflammation in the CNS and disease recovery via Fas/Fas ligand-induced apoptosis of encephalitogenic T cells, and a quick resolution of inflammation in the CNS is essential to prevent permanent damage to the CNS resulting in chronic disease.

Animals↗
PubMed2005

Matrix metalloproteinase-8 deficiency promotes granulocytic allergen-induced airway inflammation.

Matrix metalloproteinases (MMPs) are involved in inflammatory reaction, including asthma-related airway inflammation. MMP-8, mainly produced by neutrophils, has recently been reported to be increased in the bronchoalveolar lavage fluid (BALF) from asthmatic patients. To evaluate the role of MMP-8 in asthma, we measured MMP-8 expression in lung tissue in an OVA-sensitized mouse model of asthma and addressed the effect of MMP-8 deletion on allergen-induced bronchial inflammation. MMP-8 production was increased in lungs from C57BL/6 mice exposed to allergens. After allergen exposure, MMP-8(-/-) mice developed an airway inflammation characterized by an increased neutrophilic inflammation in BALF and an increased neutrophilic and eosinophilic infiltration in the airway walls. MMP-8 deficiency was associated with increased levels of IL-4 and anti-OVA IgE and IgG1 in BALF and serum, respectively. Although allergen exposure induced an enhancement of LPS-induced CXC chemokine, KC, and MIP-2 levels in BALF and lung parenchyma, no difference was observed between the two genotypes. Inflammatory cell apoptosis was reduced in the lungs from MMP-8(-/-) mice. For the first time, our study evidences an important role of MMP-8 in the control of neutrophilic and eosinophilic infiltration during allergen-induced lung inflammation, and demonstrates that the anti-inflammatory effect of MMP-8 is partly due to a regulation of inflammatory cell apoptosis.

Allergens↗
PubMed2005

TGF-beta and Smad3 signaling link inflammation to chronic fibrogenesis.

Transient adenovirus-mediated gene transfer of IL-1beta (AdIL-1beta), a proinflammatory cytokine, induces marked inflammation and severe and progressive fibrosis in rat lungs. This is associated with an increase in TGF-beta1 concentration in bronchoalveolar lavage (BAL) fluid. TGF-beta1 is a key cytokine in the process of fibrogenesis, using intracellular signaling pathways involving Smad2 and Smad3. In this study we investigate whether inflammation induced by IL-1beta is able to independently induce lung fibrosis in mice deficient in the Smad3 gene. Seven days after AdIL-1beta administration, similar levels of IL-1beta transgene are seen in BAL in both wild-type (WT) and knockout (KO) mice, and BAL cell profiles demonstrated a similar marked neutrophilic inflammation. Phospho-Smad2 staining was positive in areas of inflammation in both WT and KO mice at day 7. By day 35 after transient IL-1beta expression, WT mice showed marked fibrosis in peribronchial areas, quantified by picrosirius red staining and morphometry. However, there was no evidence of fibrosis or collagen accumulation in IL-1beta-treated KO mice, and peribronchial areas were not different from KO mice treated with the control adenovector. TGF-beta1 and phospho-Smad2 were strongly positive at day 35 in fibrotic areas observed in WT mice, but no such staining was detectable in KO mice. The IL-1beta-induced chronic fibrotic response in mouse lungs is dependent on Smad3. KO and WT animals demonstrated a similar inflammatory response to overexpression of IL-1beta indicating that inflammation must link to the Smad3 pathway, likely through TGF-beta, to induce progressive fibrosis.

Activin Receptors, Type I↗
PubMed2006

Allergic airway inflammation inhibits pulmonary antibacterial host defense.

The innate immune system of the lung is a multicomponent host defense system and in addition has an instructing role in regulating the quality and quantity of the adaptive immune response. When the interaction between innate and adaptive immunity is disturbed, pathological conditions such as asthma can develop. It was the aim of the study to investigate the effect of the allergic inflammation of the lung on the innate host defense during bacterial infection. Human bronchial epithelial cells were preincubated with Th2 cytokines and infected with Pseudomonas aeruginosa. The effect of the Th2 cytokines on the mRNA levels of antimicrobial peptides and the antimicrobial activity of HBEC was determined. To investigate the influence of an allergic inflammation on pulmonary host defense in vivo, mice sensitized and challenged with OVA were infected with P. aeruginosa, and the number of viable bacteria in the lungs was determined together with markers of inflammation like cytokines and antimicrobial peptides. Exposure of airway epithelial cells to Th2 cytokines resulted in a significantly decreased antimicrobial activity of the cells and in suppressed mRNA levels of the antimicrobial peptide human beta-defensin 2. Furthermore, mice with allergic airway inflammation had significantly more viable bacteria in their lungs after infection. This was consistent with reduced levels of proinflammatory cytokines and of the antimicrobial peptide cathelin-related antimicrobial peptide. These results show that an allergic airway inflammation suppresses the innate antimicrobial host defense. The adaptive immune system modulates the functions of the pulmonary innate immune system.

Allergens↗
PubMed2004

The roles of cytokines, inflammation and immunity in vascular diseases.

Recent findings regarding the roles of cytokines, inflammation and immunity during the development of atherosclerosis were reviewed. Especially, the relationships among pro-inflammatory cytokines such as interleukin (IL)-1, IL-18 and osteopontin, and anti-inflammatory cytokines such as IL-1 receptor antagonist, IL-10 and IL-18 binding protein to inflammation and atherosclerosis were investigated and are described in detail. In addition, helicobacter pylori and C pneumoniae infections to inflammations regarding the persistence of inflammation have been pointed out. A pro-inflammatory genotype or haplotype and toll-like receptors have been shown to be involved in human atherosclerosis. Atherosclerosis might therefore be a specific form of the chronic inflammatory process. In addition to hyperlipidemia, infections, cytokines and immunity might also be involved in the development of atherosclerosis. Certain treatments that reduce coronary risk also limit inflammation. Statins possess multiple pleiotropic effects such as an anti-inflammatory effect in addition to a lipid-lowering effect.

Cytokines↗
PubMedDate not supplied

Does a high peritoneal transport rate reflect a state of chronic inflammation?

OBJECTIVE: It has recently been reported that a high peritoneal transport rate was associated with increased mortality in continuous ambulatory peritoneal dialysis (CAPD) patients. One possible explanation is that a high peritoneal transport rate might be caused by a state of chronic inflammation, which also per se might result in increased mortality. Therefore, in this study we investigated whether high peritoneal transport rate patients are in a state of chronic inflammation. METHODS: The study included 39 clinically stable peritoneal dialysis patients (free of peritonitis) who had been on PD for more than 3 months (16.8+/-11.8 months). Seven patients were treated with continuous cycling peritoneal dialysis (CCPD) and the others were on CAPD. A 4-hour standard peritoneal equilibration test (PET) using 2.27% glucose solution was performed in each patient. Dialysate samples at 4 hours and blood samples at 2 hours were measured for interleukin-1beta (IL-1beta), tumor necrosis factor(alpha)(TNFalpha), C-reactive protein (CRP), and hyaluronan as markers of inflammation. RESULTS: There was no significant correlation between dialysate/plasma (DIP) creatinine (0.82+/-0.15, range 0.51 - 1.15) and blood concentrations of IL-1beta (11.2 ng/L, range <5 - 65.9 ng/L),TNFalpha (12.1 ng/L, range <5 - 85.4 ng/L), CRP (<10 mg/L, range <10 - 76 mg/L), nor with the blood hyaluronan concentration (165 microg/L, range 55 - 955 microg/L). The dialysate concentrations of IL-1beta and TNFalpha were below the detectable level in most of the samples. Although dialysate hyaluronan concentration (334 microg/L, range 89 - 1100 microg/L) was correlated with D/P creatinine (r= 0.36, p< 0.05), there was no correlation between the total amount of hyaluronan in the effluent and D/P creatinine. However, a significant correlation was found between serum hyaluronan concentration and glomerular filtration rate (GFR) (r = -0.49, p< 0.005); GFR also tended to be correlated with serum TNFalpha (r = -0.31, p = 0.058) but not with serum IL-1beta and serum CRP. CONCLUSION: Our results suggest that a high peritoneal transport rate is not necessarily related to a state of chronic inflammation in CAPD patients. The high mortality rate observed in high transporters may relate to other issues, such as fluid balance or abnormal nutrition and metabolism, rather than to chronic inflammation.

Biological Transport↗
PubMed1999

Role of mast cells as a trigger of inflammation in Helicobacter pylori infection.

Helicobacter pylori (H. pylori) induces severe inflammation and plays a key role in gastric mucosal diseases. In general, mast cells have been believed to play an important role in inflammation. Although mast cells were detected in the gastric mucosa, the role of mast cells in the gastric mucosal inflammation caused by H. pylori is still unclear. Therefore, we examined the effects of H. pylori water extract on the degranulation of mast cells to clarify the role of these cells in gastric mucosal inflammation induced by H. pylori. Mast cells prepared from rat abdominal cavity were incubated with H. pylori for 30 min. The protein concentrations of H. pylori water extract used in this study were 0.5-3 mg/ml. The degranulation of mast cells were monitored morphologically by phase contrast microscopy equipped with time-lapse video recording system and biochemically by measuring histamine and beta-hexosaminidase. H. pylori water extract induced the degranulation of mast cells dose-dependently. The identical experiment was performed without extracellular calcium, and no significant degranulation was found. The data indicates that the degranulation of mast cells by H. pylori water extract depend on extracellular calcium. The present results indicate that H. pylori might be involved in the gastric mucosal inflammation as a trigger of mast cell degranulation for releasing chemical mediators.

Albinism↗
PubMed1999

Role of inflammation in the pathogenesis of unstable coronary artery diseases.

Inflammation has been shown to play a pivotal role in ischemic heart disease, in particular unstable angina. The instability that characterizes this syndrome is related to the waxing and waning of ischemic stimuli, especially thrombotic ones. Angiographically and autoptically the severity of the atherosclerotic background in unstable angina does not differ from that in chronic stable angina, but in the former mural thrombi are often found and coronary atherosclerotic plaques are characterized by an inflammatory infiltrate, mostly consisting of activated lymphocytes, macrophages and mast-cells. In addition to these local findings, systemic evidence also suggests the importance of the role of inflammation in unstable angina as platelets, neutrophils and monocytes are activated, and elevated levels of serum markers of inflammation, e.g. C-Reactive Protein, have been consistently found. CRP has been demonstrated to be a reliable marker of prognosis in coronary heart disease. The consequences of inflammation are a disruption in the dynamic balance between antithrombotic and prothrombotic activities, an altered extracellular matrix metabolism, hyper-reactivity of cells such as monocytes and smooth muscle cells, all important features of unstable angina. These findings have important prognostic implications, since markers of inflammation are associated to a worse prognosis, and may also have therapeutic implications in the near future.

Angina, Unstable↗
PubMed1975

Inflammation and its effect on the vitreous.

The role of the vitreous in inflammatory diseases of the eye is now more clearly defined because of improved methods of examination and surgery. Inflammatory diseases of various aetiology produce opacification, liquefaction, and shrinkage. Additional changes include cellular proliferation and transformation leading to fibrosis in cases of prolonged inflammation. In some eyes the fibrosis is primarily cortical while in others it is extensive. Those inflammations with outpouring of a fluid exudate lead to detachment of the vitreous from the posterior eye and extensive shrinkage. In such eyes the vitreous becomes heavily organized and opaque in the central eye behind the lens, obscuring the view of the posterior fundus. In young eyes vitreo-retinal adhesions often form at the sites of inflammation, leading to traction on the retina and ciliary body; retinal tears may result from the traction. Exudate in many inflammatory vitreal inflammations tends to collect at the vitreous base where it organizes into scar tissue. The scar is formed by the retina and ciliary body, but there are also fibrosis-produced monocytes that become transformed into fibroblasts. Shrinkage of the new-formed scar can lead to disinsertion or peripheral tears of the retina. Specific inflammations such as chronic cyclitis and toxoplasmosis produce characteristic changes in the vitreous that can be recognized on clinical examination. Melanomas and reticulum cell sarcomas also produce a characteristic vitreous opacification.

Eye Diseases↗
PubMed2000

99mTc-PEG liposomes for the scintigraphic detection of infection and inflammation: clinical evaluation.

UNLABELLED: Polyethyleneglycol (PEG) liposomes have been shown to be excellent vehicles for scintigraphic imaging of infection and inflammation in various experimental models. In this article we report on a series of patients with possible infectious and inflammatory disease in whom the performance of 99mTc-PEG liposomes was evaluated. The results of 99mTc-PEG liposome scintigraphy were directly compared with those of 111In-immunoglobulin G (IgG) scintigraphy. METHODS: Thirty-five patients (22 men, 13 women; mean age, 51 y; range, 20-76 y), suspected of having infectious or inflammatory disease, received 740 MBq 99mTc-PEG liposomes intravenously. Imaging was performed at 4 and 24 h after injection. Patients received 75 MBq 111In-IgG 24 h after administration of the liposomes. The scintigraphic results were compared and verified by culture, biopsy, surgery, and follow-up of at least 6 mo. RESULTS: Of the 16 proven infections and inflammations, 15 were detected by 99mTc-PEG liposome scintigraphy: soft-tissue infection (n = 3), septic arthritis (n = 3), autoimmune polyarthritis (n = 2), infected hip prosthesis (n = 1), infected osteosynthesis (n = 1), spondylodiscitis (n = 1), infected aortic prosthesis (n = 1), colitis (n = 1), abdominal abscess (n = 1), and pneumonia (n = 1). 99mTc-PEG liposome and 111In-IgG scintigraphy both missed 1 case of endocarditis. In addition, an 111In-IgG scan of a patient with mild soft-tissue infection was false-negative. Concordantly false-positive scans were recorded from 2 patients, both with uninfected pseudarthrosis and focal signs of sterile inflammation. During liposomal administration, 1 patient experienced flushing and chest tightness, which rapidly disappeared after lowering the infusion rate. No other adverse events were observed. CONCLUSION: This clinical evaluation of 99mTc-PEG liposomes shows that focal infection and inflammation can be adequately imaged with this new agent. The performance of 99mTc-PEG liposomes is at least as effective as that of 111In-IgG. With the simple and safe preparation and the physical and logistic advantages of a 99mTc label, 99mTc-PEG liposomes could be an attractive agent for infection or inflammation imaging.

Female↗
PubMedDate not supplied

Pharmacokinetics of celecoxib in the presence and absence of interferon-induced acute inflammation in the rat: application of a novel HPLC assay.

PURPOSE: Celecoxib (CEL) is a relatively new cyclooxygenase-2 specific inhibitor nonsteroidal anti-inflammatory drug with low incidents of the toxic side effects. We developed and validated an HPLC assay for CEL and delineated pharmacokinetics of the drug in the rat in the presence and absence of inflammation. METHODS: Rat plasma (0.1 mL plasma) was spiked with CEL and ibuprofen as internal standard. The solution was acidified and constituents were extracted with isooctane-isopropanol (95:5). The organic solvent was separated, evaporated and the residue was dissolved in the HPLC mobile phase [acetonitrile-water-acetic acid-triethylamine (47:53:0.1:0.03)]. The HPLC system consisted of an auto-injector, an isocratic pump, a 10 cm C(18) analytical column packed with 5-microm of reversed-phase particles, a UV detector set at 254 nm, and an integrator. Control adult male Sprague-Dawley rats were dosed with CEL [5 mg/kg i.v. (n=8), p.o. (n=6) or i.p. (n=3)]. Acute inflammation was brought about by two (12 and 1 h pre-CEL) s.c. injection of 50,000IU/200 microL interferonalpha2a. Inflamed rats (n=6) received 5 mg oral CEL. Serial blood samples were collected via a inserted catheter at the right jugular vein, and plasma samples were analyzed for CEL. RESULTS: The assay yielded linear response within the examined ranges of 20-1000 ng/mL and 1-100 microg/mL (r(2)>0.99) with an extraction efficiency of >70%, intra- and inter-day variability of <10% and accuracy of >90%. In control rats, CEL had an oral bioavailability of 0.59 due mainly to presystemic hepatic metabolism. A multi-compartmental disposition kinetics with an average terminal t(1/2) of 2.8 +/- 0.7 h, and volume of distribution of 2.3 +/- 0.6 L/kg were found. Acute inflammation had no significant effect on the pharmacokinetics of CEL, although a trend towards increased plasma concentration was noticed. CONCLUSIONS: The validated assay has sufficient accuracy and precision for pharmacokinetic studies of CEL in the rat. The lack of change in CEL pharmacokinetics after acute inflammation maybe due to 1) insensitivity of its metabolic system to the acknowledged inhibitory effect of inflammation, and/or 2) the relatively low pre-systemic metabolism of the drug.

Acute Disease↗
PubMed2001

Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors.

Nonsteroid anti-inflammatory drugs (NSAIDs) are major drugs against inflammation and pain. They are well known inhibitors of cyclooxygenases (COXs). However, many studies indicate that they may also act on other targets. Acidosis is observed in inflammatory conditions such as chronic joint inflammation, in tumors and after ischemia, and greatly contributes to pain and hyperalgesia. Administration of NSAIDs reduces low-pH-induced pain. The acid sensitivity of nociceptors is associated with activation of H(+)-gated ion channels. Several of these, cloned recently, correspond to the acid-sensing ion channels (ASICs) and others to the vanilloid receptor family. This paper shows (1) that ASIC mRNAs are present in many small sensory neurons along with substance P and isolectin B4 and that, in case of inflammation, ASIC1a appears in some larger Abeta fibers, (2) that NSAIDs prevent the large increase of ASIC expression in sensory neurons induced by inflammation, and (3) that NSAIDs such as aspirin, diclofenac, and flurbiprofen directly inhibit ASIC currents on sensory neurons and when cloned ASICs are heterologously expressed. These results suggest that the combined capacity to block COXs and inhibit both inflammation-induced expression and activity of ASICs present in nociceptors is an important factor in the action of NSAIDs against pain.

Acid Sensing Ion Channels↗
PubMed2001

[GM-CSF in the culture supernatants of neutrophils and serum levels in patients with inflammation and squamous cell carcinoma of oral cavity].

The aim of this study was to comparison GM-CSF concentrations in the culture supernatants of neutrophils (unstimulated and LPS-stimulated) and the serum of patients with inflammation and squamous cell carcinoma of oral cavity. PMN from both patient groups exhibited decreased the ability to release of GM-CSF. PMN from patients with inflammation secreted a lower concentrations of GM-CSF than those from cancer patients. PMN from patients with inflammation were more reactivity after LPS-stimulation in comparison with cells from cancer group. GM-CSF serum levels in patients with inflammation and cancer were nonsignificantly higher in comparison with control. There was no correlation between GM-CSF in the culture supernatants of PMN and the serum levels in patient groups. The decreased GM-CSF production may lead to unfavourable effects for immune response of patients with inflammation as well as patients with cancer disease.

Adult↗
PubMed1975

[Sephadex induced inflammation in rats (author's transl)].

QUESTION: A single s.c. injection of Dextran is very suitable in producing an inflammatory response in the rat. The Dextran edema has become a standard method. It seems not uhlikely that Sephadex, the Dextran gel widely used in the gelchromatography may have a similar effect. Sephadex, because of its physiochemical properties, would offer some advantages in the studies of inflammatory reactions. But first of all the following questions have to be answered: 1. Does one single s.c. injection of Sephadex produce an inflammation at all and what are the characteristics on the microscopical level? 2 Does it make any difference if Sephadex of different types are injected? MATERIAL AND METHODS: Male and female Wistar rats (100-250 g) in groups of 5 animals each. Diet: Rat pellets "Tagger" and tap water ad libitum. Sephadex (Pharmacia Fine Chemicals) of the types G-25 m, G-50 m, G-100, and G-200 were soaked in 0.9% saline for the prescribed time and afterwards preserved until the Sephadex gel had settled on the bottom of the vessels. 1 ml of this Sephadex gel slurry each were subcutaneously injected to the shaved dorsal skin of the rats (right below). At different intervals (3, 6, 24 and 72 hours: 6, 14, 20 and 28 days) the Sephadex depot and the surrounding tissue were exstirpated and examined histologically. During all the procedures the animals were subjected to ether anesthesia. From the tissue samples frozen sections (Kryocut, -30 degrees C) were prepared and stained with hematoxylin and eosin or after van Gieson. Moreover, several preparations were stained after Pappenheim and Weigert (fibrin) or with PAS and toluidine blue. For recording of probable differences in the effect of the particular Sephadex types always 2 values were determined histometrically. The number of exudate cells emigrated between the Sephadex beads within the area of an ocular-net (edge length 1.66 mm) were counted at 500-fold magnification. Furthermore, the number of eosinophils was determined by the technique. However, because of poor occurrence the eosinophils were counted in 10 fields of view. Tests with Sephadex G-10 were omitted as preliminary tests had shown that it is not suitable for s.c. injections because of its gritty consistency (due to poor soaking properties). RESULTS: One single s.c. injection of Sephadex in the rat induces an acute inflammation. The exudative phase marked by a massive leucocytic infiltration (especially PMN leucocytes) is followed by the appearance of mononuclear leucocytes and fibroblasts after the 2nd day. The inflammation declines within approximately 3 weeks. Thereafter the Sephadex depot is encapsulated by a fibrous tissue. A chronic inflammation was never observed. In the microscopical aspect of the inflammation produced by the different types of Sephadex were detectable. The Sephadex lying in the tissue does not change its original shape, it is insoluble and is not disintegrated. The size of the particles prevents the transport into the blood or lymph vessels...

Animals↗
PubMed2002

[Mechanisms of inflammation of the respiratory mucosa].

A UNIVERSAL UBIQUITOUS PHENOMENON: Because it involves many different species, inflammation is a universal phenomenon. It is also an ubiquitous phenomenon because several organs may be involved within a given species. In humans, where it is involved in almost all pathological conditions, inflammation reaches its highest degree of complexity. FOUR STEPS: Despite the diversity of symptoms and the complexity of the molecular interactions, the sequence of events leading to an inflammatory reaction involves four steps. The first is the appearance of signals initiating inflammation. The second step involves a series of cellular reactions, the earliest reactions leading to surface phenomenon. Limitation, or on the contrary amplification, of the initial inflammatory response is the third step. Finally, healing or installation of chronic inflammation is the fourth step. Transcription factors which play a switching role in cell signaling can also be useful as therapeutic targets for anti-inflammatory agents. Two transcription factors play an important role in airway inflammation: nuclear factor NF-kappa B and activating protein 1 (AP-1). Apoptosis or programmed cell death involves a cascade of events leading to condensation of the chromatin and fragmentation of the deoxyribonucleic acid. Programmed cell death is required to resolve the inflammatory process. The principal factors involved in apoptosis can be schematically divided into pro-apoptotic factors and anti-apoptotic factors.

Animals↗
PubMed2002

Dehydroepiandrosterone attenuates allergic airway inflammation in Dermatophagoides farinae-sensitized mice.

Dehydroepiandrosterone, an androgen abundant in circulation, has important immunomodulating effects. In this study the therapeutic effect of dehydroepiandrosterone on established allergic inflammation was examined in a dust mite (Dermatophagoides farinae)-induced asthma model. Airway inflammation was provoked in D. farinae-sensitized BALB/c mice by repetitive intratracheal challenge (3 times, once a week). Three days after the first challenge, mice were fed a diet incorporated with 1.5% (w/w) dehydroepiandrosterone and were examined at days 3 and 6 after the last challenge. Airway challenge resulted in pulmonary eosinophilic inflammation accompanied by elevated blood eosinophil counts and elevated serum and bronchoalveolar lavage immunoglobulin E antibody levels in control diet-fed mice. However, the D. farinae-induced airway inflammation and blood eosinophilia was significantly reduced in dehydroepiandrosterone-fed mice, which was associated with a decrease in serum interleukin-4, interleukin-5, and interferon-gamma levels. Total immunoglobulin E antibody concentrations in serum and bronchoalveolar lavage fluids were not affected by the dehydroepiandrosterone treatment. These results demonstrated that dehydroepiandrosterone could suppress preexisting allergic airway inflammation.

Animals↗
PubMed2002

[Biodistribution of low-molecular-weight proteins and technetium (99mTc) labeled peptides in an animal model of inflammation].

The aim of this study was to evaluate accumulation of the low molecular peptides and proteins labelled with 99mTc in rat inflammatory/infection foci. Peptides (human leukocyte dialysate--HLD, thymosin fraction 5--TF5, aprotinin--APT), proteins (human IgG-HIG) were labelled with 99mTc using a redox polymer. The labelling efficiency was evaluated using paper, TLC and/or column chromatography and electrophoresis. The biodistribution of the labelled substances was evaluated in Wistar rats with Staphylococcus aureus infection or with sterile kaolin suspension-induced inflammation in the left inguinal region 24 h after abscess induction. Accumulation of 99mTc activity was determined both by external gamma camera imaging and by counting dissected tissues 1-4 hours after administration. The evaluated peptides and proteins show a high labelling efficiency (99mTc-HLD > 98%, 99mTc-TF5 > 95%, 99mTc-APT > 98%, 99mTc-HIG > 95%). Use of redox polymer for labelling raises the stability of 99mTc-labelled substances so that the labelling efficiency remains to be virtually the same (95-98%) after 8 hours at least. In experimentally induced inflammation, the amount of 99mTc-peptides and 99mTc-HIG activity accumulated is 2.5-6.5 and 5.3-10.6 times, respectively, that in control tissue. A comparison of two types of model inflammations(inflammation induced by kaolin and Staphylococcus-induced inflammation) revealed the values measured with 99mTc-peptides are more than a double that induced by kaolin suspension. The studied low molecular peptides labelled with 99mTc allow rapid localisation of infection foci in the animal model. 99mTc labelled HIG seems to be useful for the detection of both infections and inflammatory lesions.

Abscess↗