Sean David Paulsen and Dr. Allan M. Judd, Zoology
Recent neuroimmunoendocrine research has focused on points of convergence between what have traditionally been labeled the “nervous,” “immune,” and “endocrine” systems. We are beginning to realize that the walls marking the boundaries of these systems are not as exclusive as once thought. Certain commonalities or areas of overlap exist. One such point of convergence between the endocrine and immune systems is the cytokine interleukin-6 (IL-6).
Rat adrenal cells secrete interleukin-6 in response to a number of secretagogues, including the prostaglandin PGE2. At present, the mechanism for the release of EL-6 is unclear. This study builds on previous studies to analyze the general pathway for IL-6 secretion and further clarify the responses of adrenal cells to various EL-6 secretagogues. Additionally, the presence of cyclooxygenase mRNA, cyclooxygenase being an enzyme important in prostaglandin synthesis, was studied.
IL-6 MRNA and cyclooxygenase niRNA content of rat adrenal cells stimulated with lipopolysaccharide (LPS) in vivo was determined by Northern blot analysis (figures 1 and 2) and found to increase significantly.
Primary cultures of rat adrenal cells were prepared by enzymatic techniques and cultured for 4-5 days. The cells were then exposed to serum-free RPMI 1640 incubation medium containing medium and selected agents known to cause IL-6 release: adrenocorticotropic hormone (ACTH), adenosine, dopamine, interleukin-l (IL-1), LPS, serotonin, and tumor necrosis factor (TNF). Following incubation, the medium was removed from the cells, the IL-6 content of the medium was measured with the 7TD 1 bioassay, and the IL-6 mRNA content was determined by slot blot analysis. All agents studied significantly increased both cellular IL-6 mRNA concentration and IL-6 secretion (figure 3). Time dependent increases in cellular IL-6 mRNA content and IL-6 secretion suggest that IL-6 release by rat adrenal cells is transcriptionally controlled (figure 4).
Because IL-6 release is stimulated by a wide variety of chemical agents, there is an important convergence of various signals in the adrenal gland. Previous studies show that IL-6 directly modifies adrenal steroid release. Adrenal steroids are important for maintaining proper blood salt concentrations, controlling the inflammatory response, and stimulating certain metabolic changes during times of stress. The regulation of IL-6 and other cytokines systemically and in the adrenal gland may be significant in understanding septic shock, characterized by low concentrations of aldosterone and glucocorticoids, products of the adrenal cortex.