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PubMed2006

Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract.

The cytokine interleukin (IL) 25 has been implicated in the initiation of type 2 immunity by driving the expression of type 2 cytokines such as IL-5 and IL-13, although its role in the regulation of immunity and infection-induced inflammation is unknown. Here, we identify a dual function for IL-25: first, in promoting type 2 cytokine-dependent immunity to gastrointestinal helminth infection and, second, in limiting proinflammatory cytokine production and chronic intestinal inflammation. Treatment of genetically susceptible mice with exogenous IL-25 promoted type 2 cytokine responses and immunity to Trichuris. IL-25 was constitutively expressed by CD4+ and CD8+ T cells in the gut of mouse strains that are resistant to Trichuris, and IL-25-deficient mice on a genetically resistant background failed to develop a type 2 immune response or eradicate infection. Furthermore, chronically infected IL-25(-/-) mice developed severe infection-induced intestinal inflammation associated with heightened expression of interferon-gamma and IL-17, identifying a role for IL-25 in limiting pathologic inflammation at mucosal sites. Therefore, IL-25 is not only a critical mediator of type 2 immunity, but is also required for the regulation of inflammation in the gastrointestinal tract.

Animals↗
PubMed2005

Electroacupuncture attenuates inflammation in a rat model.

BACKGROUND: Acupuncture has traditionally been used in China and is being increasingly applied in Western countries to treat a variety of conditions, including inflammatory disease. However, clinical trials investigating the effectiveness of the anti-inflammatory effects of acupuncture have yielded inconsistent results, and the underlying mechanisms of acupuncture-produced anti-inflammation are unclear. OBJECTIVE: To evaluate the effectiveness of electroacupuncture (EA) on inflammation in a rat model. MATERIALS AND METHODS: Four experiments were conducted on male Sprague-Dawley rats (n = 8-9 per group). Inflammation was induced by injecting complete Freund's adjuvant (CFA) subcutaneously into the plantar surface of one hind paw of the rat. Experiment 1: To determine the effect of EA (10 and 100 Hz) versus sham treatment on inflammation. Experiment 2: To investigate the involvement of the adrenal glands on the effect of EA treatment using adrenalectomized (ADX) rats. Experiment 3: To determine the effects of EA on plasma levels of corticosterone. Experiment 4: To determine the effects of EA treatment versus immobilization on such stress indicators as heart rate and blood pressure. RESULTS: At 10 Hz EA significantly reduced CFA-induced hind paw edema. The effect was partially blocked in the ADX rats. EA significantly increased plasma levels of corticosterone but produced no noticeable signs of stress. CONCLUSION: At 10 Hz but not 100 Hz, EA suppresses inflammation by activating the hypothalamus-pituitary-adrenal axis (HPA) and the nervous system.

Analysis of Variance↗
PubMed2005

Effects of an acetone extract of Boswellia carterii Birdw. (Burseraceae) gum resin on rats with persistent inflammation.

OBJECTIVE: Ruxiang, or Gummi olibanum, an herbal medicine derived from the gum resin of Boswellia carterii Birdw. (BC) of the family Burseraceae, has been used traditionally in China to alleviate pain and reduce inflammation. The present study is an investigation of the effects of a BC extract on persistent hyperalgesia and edema in rats with peripheral inflammation. DESIGN: In this randomized, blinded study, the antihyperalgesic and antiedema effects of 3 dosages of BC were compared to a vehicle control. Inflammation was induced in rats by injecting complete Freund's adjuvant (CFA) into one hind paw. A single oral dose of the BC extract was administered daily for 7 days, beginning one day before CFA. Hyperalgesia was assessed using a paw withdrawal latency (PWL) test pre-CFA and 2 hours, 5 hours, 1 day, and 5 days post-CFA. Edema was determined by measuring paw thickness at the same time points. Spinal Fos protein expression was analyzed 2 hours post-CFA. Adverse effects of the extract were monitored by observing the animals closely for unusual behavioral changes. RESULTS: Compared to control, a dosage of 0.45 g/kg BC significantly lengthened PWL and reduced paw edema on day 5 post-CFA. At 0.90 g/kg, BC significantly lengthened PWL at 5 hours, 1 day, and 5 days, and reduced paw edema at 2 hours, 5 hours, 1 day, and 5 days. This dosage also significantly suppressed spinal Fos expression in the medial half of laminae I-II. At 1.80 g/kg, BC significantly lengthened PWL and reduced paw edema at all time points. No noticeable adverse effects were observed in animals given the lower dosages of BC, but adverse effects in some animals were observed at 1.80 g/kg per day. In the acute toxicity study, the maximal single dose of 2.50 g/kg produced no adverse effects in the treated rats during the 14 days of observation. CONCLUSIONS: The data suggest that BC produces significant antihyperalgesia and anti-inflammation effects and that the antihyperalgesia may be mediated by suppressed inflammation-induced Fos expression in the spinal dorsal horn neurons.

Analgesics↗
PubMed2005

The effect of the degree of histologic inflammation on gallbladder perforation during laparoscopic cholecystectomy.

PURPOSE: Laparoscopic cholecystectomy (LC) is the gold standard operation for the treatment of symptomatic gallstones. Intraoperative gallbladder perforation is a common complication encountered during the surgery. The purpose of this study was to identify the effects of inflammation on gallbladder perforation during LC. METHODS: Between July 1997 and March 2003, 509 patients underwent LC for symptomatic gallstone disease at the Department of Surgery at Vakif Gureba Training Hospital. Data were collected retrospectively. Patients with and without gallbladder perforation were compared in terms of gender, age, anatomic difficulty, experience of the surgeon, omental and other organ adhesions to the gallbladder, and the findings of inflammation on the resected gallbladder. RESULTS: Intraoperative gallbladder perforation occurred in 85 patients (16.6%). Although no differences were found between the perforated and nonperforated groups regarding age, gender, and chronic inflammation on the resected gallbladder, there were significant differences in terms of acute inflammation, anatomical difficulty, experience of the surgeon, and omental and organ adhesions. CONCLUSION: Acute inflammation, degree of anatomic difficulty, the experience of the surgeon, and omental or other organ adhesions were associated with gallbladder perforation during LC.

Adult↗
PubMed2004

Appetite and inflammation, nutrition, anemia, and clinical outcome in hemodialysis patients.

BACKGROUND: Malnutrition-inflammation complex syndrome, an outcome predictor in maintenance hemodialysis (MHD) patients, may be related to anorexia. OBJECTIVES: We examined whether subjectively reported appetite is associated with adverse conditions and increased morbidity and mortality in MHD patients. DESIGN: A cohort of 331 MHD outpatients was asked to rate their recent appetite status on a scale from 1 to 4 (very good, good, fair, and poor appetite, respectively). Anemia indexes and nutritional and inflammatory markers-including serum concentrations of C-reactive protein, tumor necrosis factor alpha, and interleukin 6-were measured. The malnutrition-inflammation score was used to evaluate the malnutrition-inflammation complex syndrome, and the SF36 questionnaire was used to assess quality of life (QoL). Mortality and hospitalization were followed prospectively for up to 12 mo. RESULTS: Patients were aged 54.5 +/- 14.4 y. Diminished appetite (fair to poor) was reported by 124 patients (38%). Hemoglobin, protein intake, and QoL scores were progressively lower, whereas markers of inflammation, malnutrition-inflammation scores, and the required erythropoietin dose were higher across the worsening categories of appetite. The adjusted odds ratios of diminished versus normal appetite for increased serum tumor necrosis factor alpha and C-reactive protein concentrations were significant. Significant associations between a poor appetite and an increased rate of hospitalization and mortality were observed. The hazard ratio of death for diminished appetite was 4.74 (95% CI: 1.85, 12.16; P = 0.001). CONCLUSION: Diminished appetite (anorexia) is associated with higher concentrations of proinflammatory cytokines and higher levels of erythropoietin hyporesponsiveness and poor clinical outcome, including a 4-fold increase in mortality, greater hospitalization rates, and a poor QoL in MHD patients. Appetite status may yield significant insight into the clinical status of dialysis patients.

Adult↗
PubMed2005

Inflammation is associated with increased energy expenditure in patients with chronic kidney disease.

BACKGROUND: Inflammation, a clinical condition observed in patients with chronic kidney disease (CKD), may be related to increased resting energy expenditure (REE). OBJECTIVES: The main objective was to investigate the relation between inflammation and REE in patients with CKD who are not undergoing dialysis. We also aimed to analyze whether a decrease in C-reactive protein (CRP) would result in a reduction in REE. DESIGN: This study enrolled 132 patients with CKD who were not undergoing dialysis, who had creatinine clearance from 5 to 65 mL.min(-1).1.73 m(-2), and who were 53.6 +/- 16 y old; 82 (62.1%) were men. Twenty-nine patients had clinical signs of infection. REE was measured by using indirect calorimetry, and inflammation was evaluated by using high-sensitivity CRP measurement. Patients were divided according to tertiles of CRP with the following intertertile ranges: first tertile, CRP < or = 0.14 mg/dL (n = 43); second tertile, CRP 0.15-0.59 mg/dL (n = 46); and third tertile, CRP > or = 0.60 mg/dL (n = 43). REE was measured before and after treatment in 10 patients who had inflammation or infection. RESULTS: After adjustment for age, sex, and lean body mass, the REE of the third (1395 kcal/d; P = 0.02) and second (1355 kcal/d; P = 0.04) tertiles was significantly higher than that of the first tertile (1286 kcal/d). In the multiple linear regression analysis (n = 132), the independent determinants of REE were lean body mass, CRP, and age (R2 = 0.55). After treatment of infection in a subgroup of 10 patients, it was observed that a significant reduction in CRP concentration was accompanied by a significant reduction of 174 +/- 165 kcal that accounted for 13% of the initial REE. CONCLUSION: This study showed that inflammation is associated with increased REE in patients with CKD.

Anthropometry↗
PubMed2006

Contribution of IL-18-induced innate T cell activation to airway inflammation with mucus hypersecretion and airway hyperresponsiveness.

Human bronchial asthma is characterized by airway hyperresponsiveness (AHR), eosinophilic airway inflammation, mucus hypersecretion and high serum level of IgE. IL-18 was originally regarded to induce T(h)1-related cytokines from Th1 cells in the presence of IL-12. However, our previous reports clearly demonstrated that IL-18 with IL-2 promotes Th2 cytokines production from T cells and NK cells. Furthermore, IL-18 with IL-3 stimulates basophils and mast cells to produce Th2 cytokines. Thus, we examined the capacity of IL-2 and IL-18 to induce AHR, airway eosinophilic inflammation and goblet cell metaplasia. Intranasal administration of IL-2 and IL-18 induces AHR, mucus hypersecretion and eosinophilic inflammation in the lungs of naive mice. CD4+ T cells are prerequisite for this IL-2 plus IL-18-induced bronchial asthma, because CD4+ T cells-depleted or Rag-2-deficient (Rag-2-/-) mice did not develop bronchial asthma after IL-2 plus IL-18 treatment. Both STAT6-/- mice and IL-13-neutralized wild-type mice failed to develop AHR, goblet cell metaplasia and airway eosinophilic inflammation, while IL-4-/- mice almost normally developed, suggesting that IL-13 is a major causative factor and IL-4 mainly enhances the degree of AHR and eosinophilic inflammation. Both IL-4 and IL-13 equally induce eotaxin in mouse embryonic fibroblasts. However, only IL-13 blockade inhibited asthma symptoms, suggesting that IL-13 but not IL-4 is produced abundantly and plays a critical role in the pathogenesis of bronchial asthma in this model. As airway epithelial cells store robust IL-18, IL-18 might be critically involved in pathogen-induced bronchial asthma, in which pathogens stimulate epithelial cells to produce IL-18 without IL-12 induction.

Animals↗
PubMed1990

Effects of inflammation and copper intake on rat liver and erythrocyte Cu-Zn superoxide dismutase activity levels.

Stress such as inflammation produces an acute phase response that includes elevated levels of ceruloplasmin, the main copper component of plasma. Inflammatory effects on cellular copper enzyme activity levels are largely unknown. Cu-Zn superoxide dismutase (SOD) activities in liver, the main site of ceruloplasmin secretion, decreased with turpentine-induced inflammation (0.1 mL, intramuscular, leg) in rats fed any of three copper levels (adequate = 6 mg/kg, marginal = 2.5 mg/kg and deficient less than 0.5 mg/kg). Ceruloplasmin activities rose significantly with inflammation in the adequate and marginal groups but not in the deficient animals. Hepatic Cu-Zn SOD immunoreactive protein levels were unaffected by copper status or inflammatory state. Erythrocyte Cu-Zn SOD activities were influenced by dietary copper but not inflammation. An additional group of rats fed 15 mg copper/kg did not show a turpentine-induced decrease in liver Cu-Zn activity levels. Inflammatory effects on other copper enzyme activities did occur as evidenced by increases in ceruloplasmin and decreases in serum extracellular SOD. In conclusion, an acute phase response in rats increased the amount of dietary copper required to maintain hepatic Cu-Zn SOD activity at levels equal to those of nonstressed, copper-adequate rats. Rat erythrocyte Cu-Zn SOD activities provided a blood measurement reflective of copper intake with or without stress, but these values did not reflect decreases in liver Cu-Zn SOD activities after 3 d of inflammation.

Administration, Oral↗
PubMed2002

Anaemia, rHuEPO resistance, and cardiovascular disease in end-stage renal failure; links to inflammation and oxidative stress.

End-stage renal disease (ESRD) is characterized by a high mortality rate, derived largely from cardiovascular disease (CVD). In patients with ESRD, high levels of pro-inflammatory cytokines and increased oxidative stress are common features that may contribute to malnutrition, anaemia, recombinant human erythropoietin (rHuEPO) resistance, and atherosclerosis. Inflammation predicts poor outcome in ESRD. It is multifactorial in cause and, while it may reflect the underlying CVD, the acute-phase response may also contribute to both oxidative stress and progressive vascular injury. In patients with ESRD, the acute-phase response may be influenced by a number of factors unrelated to dialysis and perhaps by the dialysis procedure itself. Inflammation and the acute-phase response interact with the haematopoietic system at several levels resulting in reduced erythropoiesis, accelerated destruction of erythrocytes, and blunting of the reactive increase in erythropoietin in response to reduced haemoglobin levels. In patients with ESRD, rHuEPO resistance has been linked with inflammation, the latter of which is often associated with a state of functional iron deficiency. Patients with ESRD are thought to have a reduced capacity to handle oxidative stress. There is recent evidence that a relationship may exist between inflammation and oxidative stress and treatment of anaemia with rHuEPO. However, iron may also generate oxidative stress. Controlled trials are needed before evidence-based recommendations for the management of inflammation-induced anaemia and resistance to rHuEPO can be defined.

Anemia↗
PubMed2002

Inflammation in end-stage renal failure: could it be treated?

End-stage renal disease (ESRD) is characterized by an exceptional mortality rate, much of which is the result of cardiovascular disease (CVD). Although traditional risk factors are common in ESRD patients, they may not be sufficient alone to account for the high prevalence of CVD in this condition. Recent evidence demonstrates that chronic inflammation, a non-traditional risk factor which is observed commonly in ESRD patients, may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. The causes of inflammation in ESRD are multifactorial and, while it may reflect underlying CVD, an acute-phase reaction may also be a direct cause of vascular injury 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. Thus, it could be speculated that suppression of the vicious cycle of malnutrition, inflammation and atherosclerosis (MIA) would improve survival in dialysis patients. Recent evidence has demonstrated strong associations between inflammation and both increased oxidative stress and endothelial dysfunction in ESRD patients. As there is as yet no recognized, or even proposed, treatment for ESRD patients with chronic inflammation, it would be of obvious interest to study the long-term effect of various anti-inflammatory treatment strategies on the nutritional and cardiovascular status as well as the outcome in these patients.

Arteriosclerosis↗
PubMed2004

Malnutrition and inflammation are associated with impaired pulmonary function in patients with chronic kidney disease.

BACKGROUND: Inflammation and malnutrition are common findings in patients with chronic kidney disease (CKD). We hypothesized that in inflamed and malnourished patients, respiratory and peripheral muscle dysfunction may have significant consequences on pulmonary function. The aim of this study was to investigate possible associations between pulmonary function and inflammation and malnutrition in patients with CKD. METHODS: We studied 109 patients (63% males; 53+/-12 years) at the initiation of dialysis treatment (GFR 7.5+/-2.5 ml/min). Pulmonary function tests [forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and peak expiratory flow (PEF)] were performed and the percentages of predicted values were calculated (%FEV(1), %FVC and %PEF). Systemic inflammation, assessed by high-sensitivity C-reactive protein (hsCRP) and nutritional status assessed by subjective global assessment (SGA), lean body mass (LBM) (estimated with dual energy X-ray absorptiometry) and hand-grip strength (HGS), were evaluated at the same time. RESULTS: Significant negative correlations were found between hsCRP and the percent predicted values for all pulmonary function tests [%FEV(1) (Rho = -0.45), %FVC (Rho = -0.43) and %PEF (Rho = -0.38)], respectively. Malnourished patients defined as SGA >or=2 had lower %FEV(1) (64+/-19 vs 82+/-23%; P<0.001) and %FVC (67+/-18 vs 83+/-21%; P<0.001) than well nourished patients. Significant correlations were observed between HGS and %FVC (Rho = 0.38; P <0.001), %FEV(1) (Rho = 0.37; P<0.001) and %PEF (Rho = 0.22; P<0.05) and between LBM and %PEF (Rho = 0.20; P<0.05). Multivariate Cox analysis showed that cardiovascular disease and low %FVC were associated with poor survival. CONCLUSIONS: Impaired pulmonary function is associated with malnutrition and inflammation, and predicts mortality in CKD patients. This may reflect an impact of malnutrition and inflammation on respiratory muscle performance, leading to pulmonary dysfunction, which could influence the clinical outcome.

Adult↗
PubMed2005

Peritoneal fast transport in incident peritoneal dialysis patients is not consistently associated with systemic inflammation.

BACKGROUND: The determinants of peritoneal fast transport status at the beginning of peritoneal dialysis (PD) are still under debate. The relationship between fast transport status and inflammation or co-morbidity, and its impact on patient survival are not fully elucidated. Our objective was to investigate if fast transport status in incident patients is associated with markers of inflammation and atherosclerosis, and its relationship to patient survival. METHODS: Seventy-three incident patients on PD performed a 3.86% peritoneal equilibrium test (PET) at 4.7+/-2.7 months after starting PD. Doppler carotid wall intima-media thickness (IMT) and the presence of carotid plaque were used as markers of atherosclerosis. C-reactive protein (CRP) and serum interleukin-6 (IL-6) were evaluated as markers of systemic inflammation. Baseline plasma levels of albumin, homocysteine, lipoprotein (a) [Lp(a)] and other lipid parameters were measured. Body mass index and residual renal function (RRF) were calculated. Patients were classified with the Davies co-morbidity score. RESULTS: The dialysate-plasma creatinine ratio (D/P creatinine) was 0.75 +/- 0.10; 26% were fast transporters (D/P > or = 0.85). In comparison with other transport categories, these had similar age, body mass index and RRF, and did not present a higher co-morbidity score than non-fast transporters. IMT did not significantly differ between groups. By multiple regression analysis, baseline peritoneal small solute transport was not related to systemic inflammation biomarkers. Fast transporters did not present higher levels of CRP or serum IL-6. Plasma levels of lipids, Lp(a), calcium x phosphorus product and albumin also did not differ between groups. Similar results were obtained when patients were grouped according to mass transfer area coefficient for creatinine. Patients with more than two co-morbidities had lower levels of plasma albumin (3.6 +/- 0.58 vs 3.9 +/- 0.9 g/dl, P = 0.054), significantly higher median levels of serum IL-6 (19.3 vs 9.2 pg/ml, P = 0.003) and wider IMT (0.90 +/- 0.36 vs 0.65 +/- 0.28 mm, P = 0.017). Multivariate analysis confirmed that baseline peritoneal transport was not a significant determinant of patient survival (P = 0.848), while the co-morbidity score remained significant (hazard ratio = 3.48, 95% confidence interval = 1.29-9.38, P = 0.014). CONCLUSION: Initial fast transport was not associated with systemic inflammation and atherosclerosis. In a population with preserved RRF and absence of baseline serious co-morbidity, it was not predictive of worse prognosis. Other determinants of early peritoneal fast transport deserve investigation.

Biological Transport↗
PubMed2003

Gamma-tocopherol, but not alpha-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats.

Gamma-tocopherol (gammaT), the major form of vitamin E in U.S. diets, and its physiological metabolite 2, 7, 8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman (gamma-CEHC), in contrast to alpha-tocopherol (alphaT), the primary vitamin E in supplements, inhibit cyclooxygenase-catalyzed synthesis of prostaglandin E2 (PGE2) in activated macrophages and epithelial cells. Here we report that in carrageenan-induced inflammation in male Wistar rats, administration of gammaT (33 or 100 mg/kg) and gamma-CEHC (2 mg/pouch), but not alphaT (33 mg/kg), significantly reduced PGE2 synthesis at the site of inflammation. gammaT, but not alphaT, significantly inhibited the formation of leukotriene B4, a potent chemotactic agent synthesized by the 5-lipoxygenase of neutrophils. Although gammaT had no effect on neutrophil infiltration, it significantly attenuated the partial loss of food consumption caused by inflammation-associated discomfort. Administration of gammaT led consistently to a significant reduction of inflammation-mediated increase in 8-isoprostane, a biomarker of lipid peroxidation. gammaT at 100 mg/kg reduced TNF-alpha (65%;P=0.069), total nitrate/nitrite (40%;P=0.1), and lactate dehydrogenase activity (30%;P=0.067). Collectively, gammaT inhibits proinflammatory PGE2 and LTB4, decreases TNF-alpha, and attenuates inflammation-mediated damage. These findings provide strong evidence that gammaT shows anti-inflammatory activities in vivo that may be important for human disease prevention and therapy.

Animals↗
PubMed2003

Isoflurane pretreatment inhibits lipopolysaccharide-induced inflammation in rats.

BACKGROUND: Previous studies have indicated that volatile anesthetic pretreatment protects cells from inflammation; therefore, the authors hypothesized that pretreatment with isoflurane may attenuate the hemodynamic and pathologic changes to the vasculature that are associated with inflammation. METHODS: Rats received intravenous lipopolysaccharide or saline placebo with and without pretreatment with isoflurane (1.4% for 30 min immediately before lipopolysaccharide). Mean arterial pressure (MAP) and response to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) vasodilators were assessed hourly for 6 h. Tumor necrosis factor-alpha concentrations, arterial blood gases, and vascular histology were also determined. RESULTS: Lipopolysaccharide decreased MAP and vasodilation to acetylcholine and sodium nitroprusside. Lipopolysaccharide also caused acidosis, endothelial swelling, and endothelial detachment from the smooth muscle. Isoflurane pretreatment prevented the decrease in MAP for 5 h and attenuated the decrease at 6 h. Pretreatment increased the vasodilation to acetylcholine in lipopolysaccharide rats to control concentrations but had no effect on sodium nitroprusside. In control rats, isoflurane pretreatment increased the response to acetylcholine and sodium nitroprusside but had no effect on MAP. Isoflurane pretreatment prevented the acidosis and endothelial damage to mesenteric and aortic vessels, and attenuated the increase in tumor necrosis factor-alpha associated with lipopolysaccharide-induced inflammation. CONCLUSION: Pretreatment with 30 min of isoflurane attenuated the decrease in MAP and endothelium-dependent vasodilation, the acidosis, the increase in tumor necrosis factor-alpha, and the damage to the vascular endothelium associated with lipopolysaccharide-induced inflammation in rats. This study suggests that isoflurane pretreatment may protect the vasculature during inflammation.

Anesthetics, Inhalation↗
PubMed2001

Activated caspase-1 is not a central mediator of inflammation in the course of ischemia-reperfusion.

BACKGROUND: Upon transplantation, donor organs subjected to prolonged ischemia suffer from reperfusion injury. Recent observations suggest that caspase activation is involved in inducing the deleterious inflammatory reaction that mediates reperfusion injury. Release of cytokines like interleukin (IL)-1 and IL-18 may occur during apoptosis through activation of caspase-1/IL-1beta-converting enzyme. We hypothesized that caspase-1 activation is a key event in apoptosis/ caspase-dependent inflammation during the development of renal reperfusion injury. METHODS: Caspase-1-/-, caspase-1+/+ as well as Swiss mice were subjected to 45 min of renal ischemia and 24 hr of reperfusion. Animals were administered agents capable of neutralizing the pro-inflammatory activation products of caspase-1 (IL-1 receptor antagonist, anti-IL-1 receptor antibody, and anti-IL-18 antibody). The extent of renal functional deterioration, inflammation, and apoptosis were compared. RESULTS: No improvement in renal function as reflected by serum ureum and creatinine were found in caspase-1-/- mice as compared to wild type controls. Caspase-1-/- mice showed slightly attenuated renal inflammation as indicated by decreased renal neutrophil influx, but failed to show changes in intrarenal tumor necrosis factor-alpha production. Moreover, caspase-1-/- mice clearly exhibited reperfusion-induced apoptosis as reflected by renal terminal deoxynucleotidyltransferase histology and internucleosomal DNA cleavage. Treatment with IL-1 receptor antagonist, anti-IL-1 receptor antibody, or anti-IL-18 antibody minimally reduced renal functional deterioration, inflammation, and apoptosis. CONCLUSIONS: These findings suggest that activated caspase-1 and its inflammatory products are involved in, but not crucial to, the induction of inflammation after renal ischemia-reperfusion. Hence, apart from caspase-1, other (combinations of) activated caspases are likely to be more prominently involved in renal reperfusion injury.

Animals↗
PubMed2001

Control of intra-ocular inflammation associated with cataract surgery.

Postoperative ocular inflammation following cataract surgery is related to the risk of complications like corneal edema, intraocular pressure spikes, cystoid macular edema, and posterior capsule opacification. The degree of postoperative inflammation following cataract surgery is linked to several surgery-dependent factors such as surgical technique, intraocular lens type, and also patient-dependent factors such as history of inflammatory disease and degree of iris pigmentation. During the past decade, major advances have occurred in cataract surgery techniques, equipment, and pharmacologic strategies that decrease the degree of postoperative inflammation following cataract surgery and reduce patients' risk for inflammation-related complications. This article reviews the most recent literature regarding the control of cataract surgery-induced intra-ocular inflammation.

Cataract Extraction↗
PubMed2005

Cochlear microperfusion: experimental evaluation of a potential new therapy for severe hearing loss caused by inflammation.

HYPOTHESIS: Cochlear microperfusion will be a useful treatment of severe sensorineural hearing loss caused by inflammation. BACKGROUND: Viruses, bacteria, and autoimmunity can initiate inflammation in the inner ear. The acute phase is associated with elevations in cytokines, nitrous oxide, and cellular infiltrates and the breakdown of the blood-labyrinthine barrier. The chronic phase leads to irreversible ossification of the labyrinth. METHODS: The authors developed cochlear microperfusion to facilitate removal of inflammatory cells and their byproducts during the acute phase of inflammation. Using a ventral approach to the guinea pig cochlea, the authors displaced resident perilymph by delivering perfusate into the scala vestibuli and collecting the effluent from the scala tympani. The authors evaluated the benefit of the procedure in an animal model of severe hearing loss caused by inflammation. RESULTS: Healthy controls undergoing cochlear microperfusion with phosphate-buffered saline incurred a mean hearing loss of 16 dB (n=4). This hearing loss was associated with the creation of two cochleostomies and not the perfusion itself. Sterile labyrinthitis (n=5) generated by perfusion of the cochlea with antigen consistently produced severe hearing loss over the initial 48 hours, and this hearing loss persisted for the subsequent 7 days. Therapeutic cochlear microperfusion, performed within the first 24 hours of developing severe hearing loss (n=9), immediately restored on average 24 dB (p <0.007) of hearing. CONCLUSION: Cochlear microperfusion is a promising new technique for treating severe deafness caused by inflammation. The benefit may be sustained when combined with local delivery of immunosuppressive agents to the inner ear.

Animals↗
PubMedDate not supplied

Chronic systemic inflammation in dialysis patients: an update on causes and consequences.

Despite marked improvements in dialysis technology during the last 20 years, the age-adjusted mortality rate in end-stage renal disease (ESRD) patients treated by 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 early stages of chronic kidney disease as compared to the general population. Although traditional risk factors for CVD 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 progressive atherosclerotic CVD and malnutrition, itself an important risk factor for the development of CVD, by several pathogenetic mechanisms. The causes of inflammation in dialysis are multifactorial and include both dialysis-related and unrelated factors. While the long-term effects of chronic inflammation may be most important in the pathogenesis of CVD, the acute-phase reaction may also cause vascular damage by several pathogenic mechanisms. Indeed, it seems logical to speculate that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) in ESRD would improve survival and decrease co-morbidity in dialysis patients. As there are currently no established guidelines for the treatment of chronic inflammation in ESRD patients, more 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 clearly warranted and will be helpful in identifying precisely which pathways are most involved in the pathogenic process.

Chronic Disease↗