Effect of atorvastatin on expression of IL-10 and TNF-α mRNA in myocardial ischemia-reperfusion injury in rats

Myocardial ischemia and reperfusion (MI/R) is associated with an intense inflammatory reaction, which may lead to myocyte injury. Because statins protect the myocardium against ischemia-reperfusion injury via a mechanism unrelated to cholesterol lowering, we hypothesized that the protective effect of statins was related to the expression of TNF-alpha (TNF-α) and interleukin-10 (IL-10) mRNA. Seventy-two rats were randomly divided into three groups as follows: sham, I/R and I/R + atorvastatin. Atorvastatin (20 mg kg⁻¹ day⁻¹) treatment was administered daily via oral gavage to rats for 2, 7 or 14 days. Ischemia was induced via a 30-min coronary occlusion. Reperfusion was allowed until 2, 7 or 14 days while atorvastatin treatment continued. We measured infarct size, hemodynamics and the plasma levels and the mRNA expression of TNF-α and IL-10 in the three groups. We demonstrated that the up-regulation of expression of both TNF-α mRNA and IL-10 mRNA was associated the increased plasma levels of TNF-α and IL-10 in the ischemic and reperfused myocardium compared with that in the sham group (P < 0.01). Atorvastatin treatment prevented ischemia-reperfusion-induced up-regulation of both TNF-α and IL-10 mRNA, and improved left ventricular function (P < 0.01). Our findings suggested that atorvastatin may attenuate MI/R and better recovery of left ventricle function following ischemia and reperfusion and IL-10 was not directly likely involved in this protective mechanism.     

Anti-IL-33 antibody treatment inhibits airway inflammation in a murine model of allergic asthma

Interleukin (IL)-33 is a recently described member of the IL-1 family and has been shown to induce production of T helper type 2 cytokines. In this study, an anti-IL-33 antibody was evaluated against pulmonary inflammation in mice sensitized and challenged with ovalbumin. The anti-IL-33 or a control antibody (150 μg/mouse) was given intraperitoneally as five doses before the sensitization and antigen challenge. Treatment with anti-IL-33 significantly reduced serum IgE secretion, the numbers of eosinophils and lymphocytes, and concentrations of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid compared with administration of a control antibody. Histological examination of lung tissue demonstrated that anti-IL-33 significantly inhibited allergen-induced lung eosinophilic inflammation and mucus hypersecretion. Our data demonstrate for the first time that anti-IL-33 antibody can prevent the development of asthma in a mouse model and indicate that blockade of IL-33 may be a new therapeutic strategy for allergic asthma.     

The dsRNA-mimetic poly (I:C) and IL-18 synergize for IFNγ and TNFα expression

Interleukin (IL)-18 bioactivity and dsRNA sensing by receptors of innate immunity are key components of anti-viral host defense. Despite extensive data on signal transduction activated by both pathways knowledge on cross-communication is incomplete. By using human PBMC and predendritic KG1 cells, as prototypic IL-18-responsive cellular models, we sought to assess cytokine production under the influence of IL-18 and the dsRNA-mimetic poly (I:C). Here, we report on potent synergy between both mediators concerning pro-inflammatory IFNγ and TNFα production. KG1 data revealed that synergistic induction likely relied on TLR3 and was associated with prolonged/increased activation of NF-κB, as detected by IκB analysis and luciferase reporter assays, respectively. Moreover, extended activation of JNK was mediated by IL-18/poly (I:C). Although vital for innate immunity, overwhelming induction of inflammatory cytokines during viral infections poses the threat of serious collateral tissue damage. The stunning synergism inherent to IL-18/dsRNA-induced TNFα/IFNγ detected herein may contribute to this pathological phenomenon.     

NEDD4-2 associates with γc and regulates its degradation rate

Interleukin-2 (IL-2) is a cytokine that regulates proliferation, differentiation and survival of various lymphoid cell subsets. Its actions are mediated through its binding to the IL-2 receptor which is composed of three subunits (IL-2Rα, IL-2Rβ and γ_c). Only β and γ_c have been shown to transduce intra cellular signals. The γ_c chain is shared by the interleukin-2, 4, 7, 9, 15 and 21 receptors, and is essential for lymphocyte functions. The regulation of γ_c expression level is therefore critical for the ability of cells to respond to these cytokines. In the present work, we show that the IL-2R constitutively associates with the ubiquitin ligase NEDD4-2, and to a lesser extent NEDD4-1. We identified the specific binding site on γ_c. And we show that the loss of NEDD4 association on γ_c is accompanied by a dramatic increase of the half-life of the receptor subunit.     

Schistosoma mansoni: Effect of dietary zinc supplement on egg granuloma in Swiss mice treated with praziqantel

Schistosomiasis is one of the most important parasitic diseases in Egypt and chemotherapy is considered the most effective method of control. This study was conducted to assess the effectiveness of zinc administration against Schistosoma mansoni infection by evaluating the activities of arylesterase and paraoxonase (PON1) enzymes, and the degree of liver damage.One hundred and twenty albino mice were divided into two groups; one was an infected control and the other a treated group which was further subdivided into three according to the praziquantel and zinc supplementation given. Blood and liver samples, collected 10 weeks post-infection, were subjected to parasitological, histopathological, and enzyme assays, and immunological studies. The results showed that dietary zinc supplementation led to marked reduction in worm load, and egg deposition in the liver and intestine.Histopathological examination showed marked reduction in the number and diameter of hepatic granulomas in the treated groups. The activity of arylesterase and PON1 enzymes were partially restored in infected animals receiving zinc. IL-10 mRNA expression was higher in the treated groups than in the infection control group. In conclusion, zinc administration could be a promising adjuvant therapy for S. mansoni infection.     

Murine NKT cells produce Th17 cytokine interleukin-22

Natural killer T (NKT) cells are known to produce Th17 cytokine IL-17 in addition to Th1/2 cytokines. In this study, the ability of NKT cells to produce IL-22, another Th17 cytokine, was examined in mice. When murine spleen cells were stimulated with α-galactosyl ceramide, a ligand for NKT cells, not only Th1/2 cytokines (IFN-γ, IL-4) but Th17 cytokines (IL-17, IL-22) were produced. NKT cells isolated from splenocytes released IL-17 and IL-22 following CD3, CD3/IL-2 or CD3/CD28 stimulation, in which CD3/CD28 costimulation was most effective. Production of IL-17 and IL-22 in CD4+ and CD8+ T cells from splenocytes was little, if any, even after CD3/CD28 costimulation. Treatment with IL-6/TGF-β decreased CD3/CD28-stimulated production of IL-22, but not that of IL-17, in NKT cells. These findings show for the first time that NKT cells are a cell source of IL-22, and that expression of two Th17 cytokines might be regulated in NKT cells by different mechanisms.