Abstract
BackgroundInterleukin-17 (IL-17)-producing cells are increasingly considered to be the major pathogenic population in various autoimmune disorders. The effects of glucocorticoids, widely used as therapeutics for inflammatory and autoimmune disorders, on IL-17 generation have not been thoroughly investigated so far. Therefore, we have explored the influence of methylprednisolone (MP) on IL-17 expression in rat lymphocytes, and compared it to the effect of the drug on interferon (IFN)-γ.ResultsProduction of IL-17 in mitogen-stimulated lymph node cells (LNC) from non-treated rats, as well as in myelin basic protein (MBP)-stimulated draining LNC from rats immunized with spinal cord homogenate and complete Freund's adjuvant was significantly reduced by MP. The reduction was dose-dependent, sustained through the follow-up period of 48 hours, and was not achieved through anti-proliferative effect. Additionally, MP inhibited IL-17 production in purified T cells as well, but to less extent than in LNC. In its influence on IL-17 production MP inhibited Ror-γT transcription factor expression, as well as Jun phosphorylation, but not ERK or p38 activation in mitogen-stimulated LNC. Importantly, MP collaborated with IFN-γ in inhibiting IL-17 generation in LNC.ConclusionThe observed difference in the effect of MP on IL-17 and IFN-γ could be important for the understanding of the variability in the efficiency of glucocorticoids in the treatment of autoimmune diseases.
Highlights
Interleukin-17 (IL-17)-producing cells are increasingly considered to be the major pathogenic population in various autoimmune disorders
IL-17 has emerged as a crucial pathogenic factor in several autoimmune and inflammatory diseases induced in experimental animals, such as experimental autoimmune encephalomyelitis (EAE), collagen induced arthritis (CIA), inflammatory bowel disease (IBD), previously thought to be mediated by Th1 cells [9]
Methylprednisolone inhibits IL-17 and IFN-γ expression in mitogen-stimulated lymph node cells Lymph node cells (LNC) isolated from Dark Agouti (DA) rats were stimulated with concanavalin A (ConA, 2.5 μg/ml) for 48 hours in the presence or absence of various methylprednisolone (MP) concentrations (0.1 – 100 ng/ml)
Summary
Interleukin-17 (IL-17)-producing cells are increasingly considered to be the major pathogenic population in various autoimmune disorders. Interleukin-17 (IL-17A or IL-17) is the prototypic member of a newly identified cytokine family which comprises five other relatives: IL-17B-F [1] This cytokine exerts its pleiotropic effects by binding to the IL-17 receptor with ubiquitous tissue and cell distribution. BMC Immunology 2008, 9:47 http://www.biomedcentral.com/1471-2172/9/47 including IL-6, IL-8, G-CSF, leukemia inhibitory factor, PGE2, nitric oxide, as well as proliferation, maturation and chemotaxis of neutrophiles [2] It is mainly produced by effector and memory CD4+ T lymphocytes developed from a unique lineage of CD4+ T cells distinct from Th1 and Th2 effectors, and negatively regulated by their respective signature cytokines IFN-γ and IL-4 [3,4]. Dysregulation of IL-17 production was found to be associated with many chronic inflammatory diseases in humans, such as rheumatoid arthritis (RA), asthma, IBD, multiple sclerosis (MS), psoriasis vulgaris, as well as with allograft rejection [10]
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