EFFECTS OF CYTOKINES ON PITUITARY BETA-ENDORPHIN AND ADRENAL CORTICOSTERONE RELEASE IN-VITRO

We investigated the effects of recombinant human IL-1 alpha, -1 beta, -2, -6 and TNF on the in vitro secretion of beta-endorphin-immunoreact ivity (beta E-IR) by the rat anterior and neurointermediate lobes (AL and NIL, respectively) and of B by the rat adrenal gland. Isolated AL and NIL cells were incubated for 2 h with cytokines (1 pg/ml-1 mu g/ml ), CRH (5.10(=10) M) or with cytokines in combination with CRH (AL cel ls), isolated adrenal cells were incubated for 2 h with cytokines, ACT H (25 pg/ml) or with cytokines in combination with ACTH. Furthermore, AL, NIL and adrenal tissue fragments were superfused for 30 or 60 min with cytokines (10 and/or 100 ng/ml). Incubation of AL, NIL and adrena l cells and superfusion of these tissues with cytokines had no signifi cant effect on beta E-TR and B release. However, there are some except ions: incubation of AL cells with IL-2 increased CRH-induced beta E-IR release, incubation of NIL cells with IL-2 induced an increase of bas al beta E-IR release. ACTH-induced B secretion was reduced after co-in cubation of adrenal cells with TNF and after prolonged (6 h) superfusi on of adrenal tissue with TNF, and finally, prolonged (6 h) superfusio n of adrenal fragments with IL-1 beta increased basal B release. Taken together, these data suggest that the acute activation of the pituita ry-adrenal axis of rats by administration of cytokines (at least IL-1, IL-6 and TNF) in vivo is not mediated by a direct action of these cyt okines at the level of the pituitary and/or adrenal gland. (C) 1996 Ac ademic Press Limited