Inhibition of the antigen activated T cell response by methylprednisolone is caused by inhibition of interleukin-2 (IL-2) production

Randazzo, B.; Hirschberg, Tom; Hirschberg, Henry

doi:10.1016/0192-0561(84)90079-1

Cited by 11 publications

(6 citation statements)

References 10 publications

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“…T lymphocytes are a major sensitive target for GC action on acquired immunity. GC counteract T cell activity by promoting their apoptosis, reducing proliferation, decreasing highaffinity IL-2 receptor-␣ chain (CD25) expression, and inhibiting IL-2 and interferon-␥ (IFN␥) production (35,38). Overall, these events cause a shift in T cell-mediated response from T helper-1 (Th1) to Th2 phenotype, which in burn-injured patients was related to impaired immunity (15).…”

mentioning

confidence: 99%

T cells from burn-injured mice demonstrate a loss of sensitivity to glucocorticoids

D’Elia

Patenaude

Dupras

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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confidence: 99%

T cells from burn-injured mice demonstrate a loss of sensitivity to glucocorticoids

D’Elia

Patenaude

Dupras

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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“…These results show that prednisolone blocks in vitro and ex vivo NKT cell expansion and suggest that the blockade is independent of APCs. While further research will be required to establish the exact mechanisms involved, the data presented here suggest it is likely to involve inhibition of IL‐2 synthesis, a well‐known effect of prednisolone (Randazzo et al , 1984; Briggs et al , 1999). IL‐2 is produced by activated NKT cells and, together with IL‐15 and IL‐7, promotes in vitro expansion of NKT cells (Metelitsa et al , 2001; van der Vliet et al , 2001).…”

Section: Resultsmentioning

confidence: 90%

“…Both APCs and conventional CD4 + and CD8 + T cells have been shown to be immunosuppressed by prednisolone treatment in vitro (Randazzo et al , 1984; Briggs et al , 1999; Vanderheyde et al , 1999). APCs and T, NK and NKT cells were pretreated separately with or without prednisolone (10 −7 mol/l) before culture with α ‐GC or vehicle (Fig 2A) to discover which subpopulation prednisolone acted upon.…”

Section: Resultsmentioning

confidence: 99%

α‐Galactosylceramide‐driven expansion of human natural killer T cells is inhibited by prednisolone treatment

et al. 2004

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SummaryThe mechanisms of action of most treatments in the autoimmune disorders are unclear and steroids remain the first-line therapy in these diseases. Natural killer T (NKT) cell activity has been implicated in the autoimmune process but whether steroids act via an affect on NKT cell function, such as antigen-specific proliferative capacity, is unknown. Immune thrombocytopenia (ITP) patients were studied ex vivo for NKT cell expansion in response to the specific NKT cell antigen, a-galactosylceramide, before, during or after prednisolone treatment. Prednisolone inhibited antigen-specific NKT cell expansion in ITP patients in remission. Untreated ITP patients also showed reduced NKT cell proliferative capacity, although this was less marked than in treated patients. These results support a role for NKT cells in ITP and aid understanding of the immunosuppressive activities of prednisolone in autoimmune disease.

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“…Corticosteroids have been shown to inhibit IL-2 production, and exogenous IL-2 reverses the inhibition of mitogen-induced T cell proliferation by corticosteroids (47)(48)(49)(50). Thus, either LTB4 or IL-2 reverses the inhibition of T cell proliferation caused by corticosteroids.…”

Section: Discussionmentioning

confidence: 99%

“…This parallels the less potent inhibition oflymphocyte proliferation by l0-M hydrocortisone (Table II). Corticosteroids have been shown to inhibit IL-2 production, and exogenous IL-2 reverses the inhibition of mitogen-induced T cell proliferation by corticosteroids (46)(47)(48)(49). To explore the relationship between LTB4 and IL-2, we examined the effect of hydrocortisone and LTB4 on IL-2 production by mitogen-stimulated T cells.…”

Section: Methodsmentioning

confidence: 99%

Mechanism of action of glucocorticosteroids. Inhibition of T cell proliferation and interleukin 2 production by hydrocortisone is reversed by leukotriene B4.

Goodwin¹,

Atluru²,

Sierakowski³

et al. 1986

J. Clin. Invest.

116

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The mechanism whereby glucocorticosteroids are immunosuppressive is unknown. One potential mechanism of action of these compounds is inhibition of arachidonic acid metabolism. We found that the inhibition of lymphocyte proliferation by hydrocortisone or dexamethasone was mimicked by nonspecific lipoxygenase inhibitors and also by a specific 5-lipoxygenase inhibitor, but not by a specific cyclooxygenase inhibitor. Mitogen-stimulated cultures of T cells produce -5 X 10-9 M leukotriene B4 (LTB4) in 24 h. This production of LTB4 is completely inhibited by concentrations of hydrocortisone or lipoxygenase inhibitors that inhibit mitogen-induced VHjthymidine incorporation. The inhibition of lymphocyte proliferation by either hydrocortisone or by the 5-lipoxygenase inhibitor was totally reversed by LTB4 but not by leukotriene C4 or leukotriene D4. LTB4 had no effect on the inhibition of lymphocyte proliferation by noncorticosteroids such as prostaglandin E2, histamine, or y-interferon. The inhibition of interleukin 2 (IL-2) production by hydroccrtisone or dexamethasone was also completely reversed by exogenous LTB4.

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Inhibition of the antigen activated T cell response by methylprednisolone is caused by inhibition of interleukin-2 (IL-2) production

Cited by 11 publications

References 10 publications

T cells from burn-injured mice demonstrate a loss of sensitivity to glucocorticoids

T cells from burn-injured mice demonstrate a loss of sensitivity to glucocorticoids

α‐Galactosylceramide‐driven expansion of human natural killer T cells is inhibited by prednisolone treatment

Mechanism of action of glucocorticosteroids. Inhibition of T cell proliferation and interleukin 2 production by hydrocortisone is reversed by leukotriene B4.

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