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-immunoreactivity (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/m1(-1) mu g/ml), CRH (5.10(-10) M) or with cytokines in combination with CRH (AL cells), isolated adrenal cells were incubated for 2 h with cytokines, ACTH (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 adrenal cells and superfusion of these tissues with cytokines had no significant effect on beta E-IR and B release. However, there are some exceptions: 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 basal beta E-IR release, ACTH-induced B secretion was reduced after co-incubation of adrenal cells with TNF and after prolonged (6 h) superfusion of adrenal tissue with TNF, and finally, prolonged (6 h) superfusion of adrenal fragments with IL-1 beta increased basal B release. Taken together, these data suggest that the acute activation of the pituitary-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 cytokines at the level of the pituitary and/or adrenal gland.
van der Meer
M J
MJ
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Hermus
A R
AR
Pesman
G J
GJ
Sweep
C G
CG
D000311:Adrenal Glands / Q000187:drug effects / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000502:physiology*; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D001615:beta-Endorphin / Q000378:metabolism*
D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone