Inflammatory Response In Experimental Model Research Articles

Aerobic and Resistant Physical Exercise on Chronic Kidney Disease (CKD) Patients: are there any Benefits?

Chronic kidney disease (CKD) has become an epidemic condition, with increasing incidence worldwide, generating high mortality rates and high health care costs. Several studies have demonstrated that inflammation is common in patients with CKD and it is associated with a high mortality rate in this population. Regular exercise has been described as a therapeutic strategy for reducing the risk of chronic and metabolic diseases, in part because of exercise training seems to exert anti-inflammatory effects. Therefore, the aim of the present review was to analyze the effects of aerobic and resistance exercise on inflammatory biomarkers in patients with CKD. CKD results in serum accumulation of toxic substances, the uremic toxins. These activate immune and inflammatory response in experimental models and in patients with CKD. Several studies involving non-pharmacological interventions have focused on CKD patients, aiming at reducing the inflammatory state, improving quality of life and extending the survival of these patients. It has been found that using treadmill for walking in patients undergoing pre-dialysis treatment was effective in reducing CRP and IL-6, showing that this type of aerobic exercise may also promote an anti-inflammatory effect. In contrast, some studies have not been able to show any beneficial effect on inflammation; e.g., a study using an intradialytic cycling protocol for HD patients 3x / week for 6 months found no decrease in IL-6, CRP and TNF-α. There are a number studies reporting favorable effects of exercise training on the inflammatory response triggered by hypertension, diabetes, obesity, dyslipidemia and cardiovascular events in the general population; however, this review showed that the role of the anti-inflammatory effect of aerobic and resistance exercise remains controversial in CKD patients, particularly in those undergoing dialysis. Conversely, data from the literature found that high intensity aerobic exercise training for a sustained period of time seems to have anti-inflammatory effects when compared to resistance exercise, in particular when PCR is used as a marker of inflammation.

Vitamin D supplementation attenuates acute inflammatory response

This study evaluated the effects of daily vitamin D supplementation on the acute inflammatory response in experimental model by different phlogistic agents: carrageenan, prostaglandin and dextran. Animals (rats) orally received (gavage) a single dose of vitamin D or daily supplementation for 7, 15 or 30 days prior to paw edema induced. Vitamin D supplementation for 15 and 30 days significantly reduced the carrageenan-induced inflammatory process, which could be at least partially explained by the reduction of tumor necrosis factor α levels (TNFα). Results indicate that vitamin D supplementation may be a useful therapeutic adjuvant for controlling the acute inflammatory process.

Beneficial effects of combination of tissue transglutaminase inhibitor and interleukin-15 inhibitor in ameliorating mucosal immune inflammatory response in experimental model of Celiac Disease

Beneficial effects of combination of tissue transglutaminase inhibitor and interleukin-15 inhibitor in ameliorating mucosal immune inflammatory response in experimental model of Celiac Disease

Role of Rifampin in Reducing Inflammation and Neuronal Damage in Childhood Bacterial Meningitis: A Pilot Randomized Controlled Trial.

Treatment of acute bacterial meningitis in children with bactericidal antibiotics causes cell wall lysis and a surge in inflammatory cascade, which in turn contributes to neuronal damage and morbidity. Pretreatment with a nonbacteriolytic antibiotic, such as rifampin, has been shown to attenuate the inflammatory response in experimental models of bacterial meningitis. In a pilot study, in children with bacterial meningitis, we have studied markers of inflammatory response and neuronal damage in 2 groups of children with bacterial meningitis; one group received rifampin pretreatment with ceftriaxone and the other group received ceftriaxone alone. Forty children with bacterial meningitis, who were 3 months to 12 years of age, were randomly assigned to receive either a single dose rifampin (20 mg/kg) 30 minutes before ceftriaxone or ceftriaxone alone was given. The primary outcome variables were cerebrospinal fluid (CSF) concentrations of tumor necrosis factor alpha (TNFα), S100B and neuron-specific enolase on day 1 and day 5, and secondary outcome variables were the values of TNFα and interleukin 6 in serum on day 1 and day 5; hearing and neurologic sequelae at 3 months after recovery from the illness. Children in rifampin pretreatment group had significantly lower CSF TNFα concentrations [median (interquartile range [IQR]): 15.5 (7.2-22.0) vs. 53.0 (9.0-87.5) pg/mL, P = 0.019] and S100B [median (IQR): 145.0 (54.7-450.0) vs. 447.5 (221.0-804.6) pg/mL, P = 0.033] on day 1 and S100B [median (IQR): 109.7 (64.0-287.0) vs. 322 (106.7-578.0) pg/mL, P = 0.048] and neuron-specific enolase [median (IQR): 8.6 (5-14.75) vs. 18.2 (7.0-28.75) ng/mL, P = 0.035] on day 5 when compared with ceftriaxone alone group. The rifampin-treated group also had reduced morbidity and neurologic sequelae; however, these were not statistically significant. Pretreatment with single dose rifampin 30 minutes before ceftriaxone administration reduced the CSF concentrations of markers of inflammation and neuronal damage in children with bacterial meningitis.

Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia-Reperfusion Injury.

Ischemia-reperfusion injury (IRI) is an important cause of acute kidney injury that can lead to end-stage renal failure. Although the ensuing inflammatory response can restore homeostasis, a consecutive maladaptive repair and persistent inflammation represent important risk factors for postischemic chronic kidney disease development. In this study, we investigated the role of mast cells in both the early and late phases of the inflammatory response in experimental models of acute and chronic renal IRI using our recently developed mouse model that allows conditional ablation of mast cells. Depletion of mast cells prior to IRI resulted in improved renal function due to diminished local inflammatory cytokine/chemokine levels and neutrophil recruitment to the kidneys after the acute injury phase (48 h post-IRI). Furthermore, although not completely protected, mast cell-depleted mice displayed less organ atrophy and fibrosis than did wild-type mice during the chronic phases (2 and 6 wk post-IRI) of disease development. Conversely, mast cell ablation after the acute phase of IRI had no impact on organ atrophy, tubular necrosis, or fibrosis. Thus, our results suggest a deleterious role of mast cells during the acute inflammatory phase of IRI promoting subsequent fibrosis development, but not during the chronic phase of the disease.

Cytokine gene expression and molecular detection of Mycobacterium avium subspecies paratuberculosisin organs of experimentally infected mice

AbstractMycobacterium avium subspecies paratuberculosis (MAP) can infect ruminants and remain subclinical for long periods within herds. The identification of organs that are more susceptible to infection and the evaluation of cytokine expression at the site of infection are important to understand the pathogenesis of MAP. In this study, the probability of detection of MAP-DNA and the expression of cytokines in organs of C57BL/6 mice infected intraperitoneally for 120 days were evaluated. Among the evaluated organs, the spleen (85%), colon (75%) and liver (60%) had the highest frequency of positivity. When compared these frequencies between organs, it has been found that the spleen had 1.54 times as likely to be positive in relation to the ileum, and 2.0 times more likely in relation to the Peyer's patches. In addition, at 60 days post-infection, the spleen and the liver were responsible for upregulation of IFN-γ , and the ileum by TNF-α and IL-4. The results indicate that the spleen is the best organ for evaluating an experimental infection by MAP, especially in the initial stages of the infection. Moreover, it showed that the spleen, liver and ileum have a direct role in the inflammatory response in experimental models.

Probiotic Administration Reduces Mortality and Improves Intestinal Epithelial Homeostasis in Experimental Sepsis

Recent clinical trials indicate that probiotic administration in critical illness has potential to reduce nosocomial infections and improve clinical outcome. However, the mechanism(s) of probiotic-mediated protection against infection and sepsis remain elusive. The authors evaluated the effects of Lactobacillus rhamnosus GG (LGG) and Bifidobacterium longum (BL) on mortality, bacterial translocation, intestinal epithelial homeostasis, and inflammatory response in experimental model of septic peritonitis. Cecal ligation and puncture (n=14 per group) or sham laparotomy (n=8 per group) were performed on 3-week-old FVB/N weanling mice treated concomitantly with LGG, BL, or vehicle (orally gavaged). At 24 h, blood and colonic tissue were collected. In survival studies, mice were given probiotics every 24 h for 7 days (LGG, n=14; BL, n=10; or vehicle, n=13; shams, n=3 per group). Probiotics significantly improved mortality after sepsis (92 vs. 57% mortality for LGG and 92 vs. 50% mortality for BL; P=0.003). Bacteremia was markedly reduced in septic mice treated with either probiotic compared with vehicle treatment (4.39±0.56 vs. 1.07±1.54; P=0.0001 for LGG; vs. 2.70±1.89; P=0.016 for BL; data are expressed as mean±SD). Sepsis in untreated mice increased colonic apoptosis and reduced colonic proliferation. Probiotics significantly reduced markers of colonic apoptosis and returned colonic proliferation to sham levels. Probiotics led to significant reductions in systemic and colonic inflammatory cytokine expression versus septic animals. Our data suggest that involvement of the protein kinase B pathway (via AKT) and down-regulation of Toll-like receptor 2/Toll-like receptor 4 via MyD88 in the colon may play mechanistic roles in the observed probiotic benefits. Our data demonstrate that probiotic administration at initiation of sepsis can improve survival in pediatric experimental sepsis. The mechanism of this protection involves prevention of systemic bacteremia, perhaps via improved intestinal epithelial homeostasis, and attenuation of the local and systemic inflammatory responses.

NutriSim© Diminishes an Endotoxin-stimulated Proinflammatory Cytokine Production

Lipopolysaccharide, a main component of Gram-negative bacterial endotoxin is the leading cause of sepsis or endotoxic shock. This condition generates tissue hypoperfusion and leads to a state of acute metabolic-circulatory dysfunction and multiorgan systemic failure which contributes to amplify the inflammatory response and resulting in the release of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6). The effect of NutriSim© on serum pro-inflammatory cytokine concentrations were investigated in lipopolysaccharide-treated male Wistar rats. Animals were randomized into five groups: control groups receiving a single intraperitoneal injection of physiologic saline solution or NutriSim© (10µl), respectively; LPS (20 mg/Kg, i.p.); NutriSim© treatment 15 min before or after LPS in the same aforementioned dose. The results showed that a single dose of NutriSim© prior or before the endotoxic insult diminishes significantly the production of serum TNF-α, IL-1 and IL-6. Therefore NutriSim© can modulate an inflammatory response in experimental model of endotoxic shock.

Fragilisation/stabilisation des plaques. Rôle de l’inflammation

Atherosclerosis is an inflammatory disease of the arterial wall that carries an important socio economic burden. The available data strongly suggest that both innate and adaptive immuno inflammatory mechanisms are the major determinants of plaque complications (called instability). Therefore, most of the important advances in the comprehension of the mechanisms of atherosclerosis came from studies that aimed at the elucidation of the critical components involved in the modulation of the immuno inflammatory response in experimental models of atherosclerosis. Since Thl-driven immune response has been consistently shown to promote atherosclerosis, the general belief is that immuno-modulation through Th2 may be suitable to halt the disease process. Here, we present a novel view of the immuno-inflammatory response in atherosclerosis where the adaptive regulatory response modulates both Thl and Th2 responses and plays a central role in counteracting disease initiation and progression.