An alternate mechanism of glucocorticoid anti-proliferative effect: promotion of a Th2 cytokine-secreting profile.
Glucocorticoids (GCs) are used as immunosuppressive and anti-inflammatory agents in organ transplantation and in treating autoimmune diseases and inflammatory disorders and they exert their effects by several mechanisms, the most significant of which is inhibition of cytokine production and action. Recent reports suggested that GCs inhibit cytokine expression indirectly through promotion of a T helper cell type 2 (Th2) cytokine-secreting profile, thereby resulting in preferential blockade of pro-inflammatory monokine and T helper cell type 1 (Th1) cytokine expression. The target of GCs appeared to be monocytes macrophages, whereby altered regulation of interleukin (IL)-1/IL-1 receptor antagonist (IL-1ra), coupled with profound blockade of IL-12 synthesis and inhibition of interferon (IFN)-gamma-induced major histocompatibility complex (MHC) class II expression, lead to a preferential cognate stimulation of Th2 cells at the expense of Th1 cells. It is possible that this may have involved the expansion of a Th2-cell pool or, in addition, frank stimulation of uncommitted naive CD4 + T cells toward the Th2 lineage. In addition, GCs may have blocked Th1 cytokine expression, thereby inhibiting ongoing Th1 cytokine secretion, and consequently provided for the unimpeded production of Th2 cytokines. Collectively, this indicates that, in exerting their anti-proliferative effects, GCs act indirectly by altering Th1/Th2 cytokine balance, blocking the (pro-inflammatory) Th1 program and favoring the (anti-inflammatory) Th2 program.
Almawi
W Y
WY
Department of Laboratory Medicine, St Georges-Orthodox Hospital, Beirut, Lebanon.
Melemedjian
O K
OK
Rieder
M J
MJ
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism* / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology*; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D013256:Steroids; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D013256:Steroids