Glucocorticoids promote a TH2 cytokine response by CD4+ T cells in vitro.
Purified rat CD4+ T cells were activated in vitro in the presence or absence of the glucocorticoid dexamethasone. They were then expanded in IL-2 and subsequently restimulated, this time in the absence of the hormone. The results indicate that the exposure of the cells to dexamethasone in the primary stimulation changed the cytokine synthesis induced by the secondary stimulation. The mRNA levels for IL-4, IL-10, and IL-13 were all increased by the pretreatment, whereas synthesis of IFN-gamma and TNF-alpha was diminished. Further studies in which IL-4 was used together with dexamethasone showed that the cytokine potentiated the effect of the hormone. These data suggest that the neuroendocrine system can influence the cytokine response to pathogens and autoantigens in a way that favors Th2-type reactions. There are similar implications for therapy with glucocorticoids, and these drugs may be expected to have long term immunologic effects as well as short-lived immunosuppressive ones. The production of a mouse mAb, MRC-OX81, against rat IL-4 is also described.
Ramírez
F
F
Medical Resarch Council, Cellular Immunology Unit, Sir William Dunn School of Pathology, University of Oxford, United Kingdom.
Fowell
D J
DJ
Puklavec
M
M
Simmonds
S
S
Mason
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D018793:Interleukin-13 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D000911:Antibodies, Monoclonal; D016207:Cytokines; D017931:DNA Primers; D005938:Glucocorticoids; D018793:Interleukin-13; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D016753:Interleukin-10; D015847:Interleukin-4; D003907:Dexamethasone; D007371:Interferon-gamma