Glucocorticoids Induce a TH2 Response In Vitro

Journal of Immunology Research, Aug 2018

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Glucocorticoids Induce a TH2 Response In Vitro

Glucocorticoids Induce a Th2 Response In Vitro FRANCISCO RAMREZ 0 0 Medical Research Council, Cellular Immunology Unit, Sir William Dunn School of Pathology, University of Oxford , South Parks Road, Oxford OX1 3RE Purified rat CD4 T cells were activated in vitro, by the polyclonal mitogen Concanavalin A (Con A) or by mixed lymphocyte reaction (MLR), in the presence or absence of the glucocorticoid dexamethasone (DEX). 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 DEX in the primary stimulation changed the cytokine synthesis induced by the secondary stimulation. IL-4 production was increased by the pretreatment whereas synthesis of IFN-y was diminished. Addition of DEX in the second activation suppressed all cytokine production. In brief, the transient presence of glucocorticoids in the culture induces a change in the pattern of cytokine production but the continuous presence causes inhibition of cytokine synthesis. Further studies in which IL-4 was used together with DEX showed that the cytokine potentiated the effect of the hormone. The data here presented suggest that glucocorticoids and the neuroendocrine system may be expected to have long-term immunological effects as well as short-lived immunosuppressive ones. High concentration of glucocorticoids suppress cytokine production but when steroids return to basal levels the immune response is directed in a way that favors Th2-type reactions. Possible implications regarding the immune response to pathogens and autoantigens are discussed. Activation; CD4 T cells; cytokines; glucocorticoids INTRODUCTION reaction (Munck et al., 1984). During the course of an immune response corticoid secretion from the adrenal Understanding the influence of glucocorticoids on the glands is increased and this mechanism limits the immune system is important for two reasons: first, magnitude of the inflammatory reaction to an immucorticosteroids are used as immunosuppressive and nogenic stimulus (Besedovsky et al., 1975) . Followanti-inflammatory agents in organ transplantation and ing activation of the immune system several soluble in the treatment of many autoimmune and inflammafactors that activate the neuroendocrine system are tory diseases. Second, it is not commonly recognised released (Besedovsky et al,., 1981) . Partial failures in that, in addition to their pharmacological actions, this interaction between the immune and neuroendothese steroids are natural hormones that play an crine systems contribute to the pathogenesis of certain essential physiological role in the regulation of the autoimmune and inflammatory experimental diseases immune system. Release of endogenous glucocorlike thyroiditis, arthritis and experimental allergic ticoids protects us against our own defense mechanisms by preventing an excessive immunological encephalomyelitis (EAE) (Kroemer et al., 1988; MacPhee et al., 1989; Sternberg et al., 1989; Mason et al., 1990) . There are also evidences that patients with rheumatoid arthritis show a defective regulation of corticosteroids production (Chikanza et al., 1992) . Our interest in the role of corticosteroids in the regulation of the immune response originated from the study of EAE in Lewis rats. EAE is an animal model of autoimmune disease, similar to multiple sclerosis, that can be induced in the appropriate animal strains after immunization with myelin basic protein (MBP) in complete Freund?s adjuvant. EAE in Lewis rats is a monophasic disease characterized by a single episode of paralysis, caused by the action of CD4 T lymphocytes on the nervous system, followed by spontaneous recovery. Animals that have recovered are refractory to attempts to induce further episodes of disease (Zamvil and Steinman, 1990) . The mechanisms responsible for the spontaneous recovery and the maintenance of the refractory state, although object of intense research, are not completely understood. One mechanism that controls the course of EAE is neuroendocrine-mediated immunoregulation. It has been shown that endogenously produced corticosterone plays an essential role in the recovery of rats from EAE: Unlike normal rats, adrenalectomized animals do not recover spontaneously but instead develop a progressive paralysis with a fatal consequence. If these animals are administered corticosterone, they recover and become refractory to the development of new episodes of disease (Levine et al., 1980; MacPhee et al., 1989) . The spontaneous recovery of rats from EAE probably occurs because corticosteroids, which are found at high levels in the sera of paralyzed animals, acutely depress the autoimmune response through their immunosuppressive effects. However, animals that have recovered from disease have normal serum steroid levels indicating that corticosteroids are not directly responsible for the maintenance of the refractory phase of the disease. (...truncated)


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Francisco Ramírez. Glucocorticoids Induce a TH2 Response In Vitro, Journal of Immunology Research, 6, DOI: 10.1155/1998/73401