Differential cytokine regulation by eicosanoids in T cells primed by contact sensitisation with TNP.
Eicosanoids are important mediators of inflammation, but also play a role in regulation of lymphocyte function. In this study we have examined the function of both prostaglandins (PGs) and leukotrienes in regulating the release of a set of cytokines produced by T cells from mice primed with the contact-sensitising agent picryl chloride. Various patterns of response by different cytokines in response to exogenous eicosanoids were observed. Both interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), two cytokines involved in activating the cellular contact sensitivity reaction, were downregulated by prostaglandin E2 (PGE2) and to a lesser extent by 6-keto PGF2 alpha (PGI2). In contrast, both PGE2 and PGI2 potentiated the release of IL-3 and IL-6 which both play an important role in stimulating haemopoesis after inflammation. Unexpectedly, IL-4 release was strongly inhibited by exogenous PGI2, while remaining unaffected by PGE2. This inhibition, in contrast to the PG-mediated effects on IL-2, IL-3, IL-6, and IFN-gamma was not due to increased intracellular levels of cAMP. In contrast to the strong immunomodulatory effects of PGs, leukotrienes B4 and C4 had only small and rather variable effects on any cytokine release.
Marcinkiewicz
J
J
Department of Biology, University College London, United Kingdom.
Chain
B M
BM
D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D016285:Iloprost / Q000494:pharmacology*; D007372:Interferons / Q000276:immunology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors; D007377:Interleukin-3 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D010851:Picrates; D010853:Picryl Chloride; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D007376:Interleukin-2; D007377:Interleukin-3; D015850:Interleukin-6; D010851:Picrates; D015847:Interleukin-4; D007372:Interferons; C005858:picric acid; D016285:Iloprost; D015232:Dinoprostone; D010853:Picryl Chloride