Rat IL4 peptide

Rheumatoid arthritis is considered a T-lymphocyte-mediated disease. However, studies have focussed on CD4 T-lymphocytes, ignoring CD8 T-lymphocytes despite the latter being found abundantly in the synovium. Specifically, there is little data of the effect of methotrexate, the gold-standard DMARD, on various CD8 cytokine T-lymphocyte subsets and conflicting data on CD4 subsets. In this prospective study, patients with active rheumatoid arthritis, who were 18 to 65years of age, were treated with methotrexate (up to 25mg per week) for 24weeks. At baseline and 24weeks, frequencies of CD8(+)IFN(+), CD8(+)IL17(+), CD8(+)IL4(+), corresponding CD4 subsets and plasma levels of IFN, IL-12, IL-10, IL-4 and IL-17 were determined by flow cytometry. These are summarised as median (IQR=interquartile range, 25th-75th percentile) and paired data compared using Wilcoxon signed rank test. This study included 67 patients (F/M=4:1) with rheumatoid arthritis, 57 (85%) being RF positive and 20 receiving prednisolone at baseline. Mean (+/- SD) dose of methotrexate at 24weeks was 22.9 +/- 3.0mg per week. On treatment with methotrexate, there was a significant (p=0.04) decline in CD8(+)IFN(+) cells from 37.2 (IQR 19.4-60.2) to 22.7% (IQR 8.5-49.7) and a marginal increase in CD8(+)IL17(+) cells from 0.3 (IQR 0.1-0.6) to 0.4 (IQR 0.2-1.2), p=0.006. There was no significant change in the other subsets. There was also a significant decline in circulating levels of IL-12, IL-10 and IL-17 and marginal increase in IL-4. On evaluating by response, non-responders but not responders had a significant increase in CD8(+)IL17(+) (p=0.01). There is a significant decline of CD8(+)IFN(+) T cells and marginal increase in CD8(+)IL17(+) T cells after methotrexate. Change in Tc1 subset may be mediated through reduction in IL-12 levels.

Purpose: Lung tissue is one of the most sensitive organs to ionizing radiation (IR). Early and late side effects of exposure to IR can limit the radiation doses delivered to tumors that are within or adjacent to this organ. Pnetunonitis and fibrosis are the main side effects of radiotherapy for this organ. IL-4 and IL-13 have a key role in the development of pneumonitis and fibrosis. Metformin is a potent anti-fibrosis and redox modulatory agent that has shown radioprotective effects. In this study, we aimed to evaluate possible upregulation of these cytokines and subsequent cascades such as IL4-R1, IL-13R1, Dual oxidase 1 (DUOX1) and DUOX2. In addition, we examined the potential protective effect of metformin in these cytokines and genes, as well as histopathological changes in rat's lung tissues. Methods: 20 rats were divided into 4 groups: control; metformin treated; radiation + metformin; and radiation. Irradiation was performed with a Co-60 source delivering 15 Gray (Gy) to the chest area. After 10 weeks, rats were sacrificed and their lung tissues were removed for histopathological, real-time PCR and ELISA assays. Results: Irradiation of lung was associated with an increase in IL-4 cytokine level, as well as the expression of IL-4 receptor-al (IL4ra1) and DUOX2 genes. However, there was no change in the level of IL-13 and its downstream gene including IL-13 receptor-a2 (IL13ra2). Moreover, histopathological evaluations showed significant infiltration of lymphocytes and macrophages, fibrosis, as well as vascular and alveolar damages. Treatment with metformin caused suppression of upregulated genes and IL-4 cytokine level, associated with amelioration of pathological changes. Conclusion: Results of this study showed remarkable pathological damages, an increase in the levels of IL-4, IL4Ra1 and Duox2, while that of IL-13 decreased. Treatment with metformin showed ability to attenuate upregulation of IL-4-DUOX2 pathway and other pathological damages to the lung after exposure to a high dose of IR.