PGE(2)-induced immunoregulation mediated by cytokine production from cultures of human peripheral T lymphocytes.

Prostaglandins (PGs) are generally known to exert inhibitory as well as some enhancing effects on the immune system. This study was performed to assess the influence of the exogenous PGs and cyclic adenosine monophosphate (cAMP)-elevating agents on cytokine production by PWM-stimulated human T lymphocytes. Peripheral blood T lymphocytes from healthy donors were pretreated for 30 min at 25 degrees C with PGE(2) (10(-4) to 10(-7) M) PGF(1 alpha), IBMX or Forskolin (10(-4) to 10(-5) M) and cultured for 7 days in the presence of Pokeweed Mitogen (PWM). PGE(2), IBMX and Forskolin, but not PGF1 alpha, significantly increased IL-6 production while inhibited IL-2, IL-3, IL-4, IFN-gamma, TNF-alpha and GM-CSF production. Our data indicate that cAMP-elevating agents can profoundly affect cytokine secretion by T cells in PWM-driven cultures and that this effect is dose-dependent. The results reported here are compatible with the existence of separate pathways of gene induction for IL-2, IL-3, IL-4, IFN-gamma, TNF-alpha and GM-CSF on the one hand and IL-6 on the other one.