Methylprednisolone inhibits interleukin-17 and interferon-gamma expression by both naive and primed T cells.
BACKGROUND
Interleukin-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)-gamma.


RESULTS
Production 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-gammaT transcription factor expression, as well as Jun phosphorylation, but not ERK or p38 activation in mitogen-stimulated LNC. Importantly, MP collaborated with IFN-gamma in inhibiting IL-17 generation in LNC.


CONCLUSIONS
The observed difference in the effect of MP on IL-17 and IFN-gamma could be important for the understanding of the variability in the efficiency of glucocorticoids in the treatment of autoimmune diseases.
Momcilović
Miljana
M
Department of Immunology, Institute for Biological Research Sinisa Stanković, Belgrade, Serbia. mommilja@eunet.yu
Miljković
Zeljka
Z
Popadić
Dusan
D
Marković
Milos
M
Savić
Emina
E
Ramić
Zorica
Z
Miljković
Djordje
D
Mostarica-Stojković
Marija
M
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D006168:Guinea Pigs; D007114:Immunization; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D008775:Methylprednisolone / Q000627:therapeutic use*; D004676:Myelin Basic Protein / Q000276:immunology / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014020:Tissue Extracts / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
D020381:Interleukin-17; D004676:Myelin Basic Protein; D014020:Tissue Extracts; D003208:Concanavalin A; D007371:Interferon-gamma; D008775:Methylprednisolone