DIFFERENTIAL RELEASE OF TUMOR-NECROSIS-FACTOR AND IL-6 FROM ADRENAL ZONA GLOMERULOSA CELLS IN-VITRO

In previous studies, rat adrenal zona glomerulosa (ZG) cells were demo nstrated to release interleukin-6 (IL-6). In the current study, cultur es of ZG cells and bioassays for tumor necrosis factor (TNF) and IL-6 were used to determine if ZG cells release TNF and to define more full y the factors that regulate ZG IL-6 release. ZG cells released IL-6 an d TNF, and this release was stimulated by lipopolysaccharide, interleu kin-1 alpha, interleukin-1 beta, a protein kinase C activator, and a c alcium ionophore without affecting intracellular adenosine 3',5'-cycli c monophosphate (cAMP) content. In contrast, adrenocorticotropic hormo ne (ACTH) increased the intracellular cAMP content, increased basal an d secretagogue-stimulated IL-6 release but decreased basal and secreta gogue-stimulated TNF release. The effects of ACTH on IL-6 and TNF rele ase may be mediated by increases in intracellular cAMP because ACTH an d dibutyryl cAMP modified IL-6 and TNF release in an identical manner. Therefore, IL-6 and TNF release from ZG cells can be differentially r egulated. Because IL-6 and TNF modify adrenal steroid release, the adr enal production of these cytokines may have a role in the stress respo nse.