Tumor necrosis factor increases interleukin-6 release from adrenal zona glomerulosa cellsin vitro

Rat adrenal zone glomerulosa cells secrete tumor necrosis factor (TNF) and interleukin-6 (IL-6). We have extended previous studies to determine if TNFα can modify the release of adrenal IL-6. Primary cultures of rat adrenal zone glomerulosa cells were prepared by enzymatic techniques and cultured for 4-6 days. The cells were then exposed to serum-free RPMI 1640 incubation medium containing vehicle (RPMI-1640 medium alone), TNFα and/or selected agents known to stimulate adrenal IL-6 release. Following a 5 h incubation, the incubation medium was removed from the cells and the IL-6 content of the medium measured with the 7TD1 bioassay. TNFα (0.5-50 ng/mL) increased basal adrenal IL-6 release in a concentration-dependent manner. Furthermore, TNFα potentiated in a more than additive manner the adrenal IL-6 release stimulated by lipopolysac-charide (LPS), interleukin-1β, angiotensin II and ACTH. TNFα potentiated the IL-6 release stimulated by a wide range of concentration of IL-lβ (0.01-100 ng/mL) and ACTH (0.1-100 nM). Because IL-6 and TNFα modify the steroid secretion from adrenal cells, these cytokines may interact together to regulate the function of the adrenal cortex.