Todd A. Richards and Dr. Allan M. Judd, Zoology
The adrenal is an endocrine gland that is important for the release of steroid hormones and cathecholamines. The adrenal gland is closely associated with the immune system. This association is closely linked by the release of cytokines. Cytokines are a diverse group of proteins first isolated within the immune system but have now been identified in numerous tissues, including those of the endocrine system. The principle cytokines affecting the adrenal gland are interleukin-1 (IL-alpha and IL-beta), interleukin-6 (IL-6) and tumor necrosis factor (TNF). These cytokines can regulate adrenal function, particularly during increased stress and disease, and because they are produced in the adrenal gland, they may be paracrine/autocrine regulators of adrenal function. Modification of adrenal function plays a role in septic shock, lupus erythematosus, cardiovascular disease, rheumatoid arthritis, throidits, aging, and HIV infection.
The adrenal gland is composed of a cortex and medulla. The cortex is composed of three zones, of which the outermost or zona glomerulosa (ZG) produces aldosterone. Aldosterone produced within the ZG is known to have importance in the regulation of sodium and potassium balance, which in turn affects the water and electrolyte balance of the organism. The salt and water balance of the organism in turn regulates blood volume and thus, blood pressure. In patients with septic shock, caused by the release of lipopolysacchride (LPS) by gram negative bacteria, an over production of cytokines causes vasodialation to occur causing a fall in blood pressure.
The tables and figures on the following pages represent seven separate experiments which were performed on the zona glomerulosa of bovine adrenals. In summary, this data provides evidence that IL-6 decreases angiotensin II-stimulated aldosterone release, but stimulates basal and ACTHstimulated aldosterone release. IL-lbeta has no apparent effect on basal aldosterone release, but similar to EL-6, decreases angiotensin II stimulated aldosterone release, but enhances ACTHstimulated aldosterone release. TNF in contrast inhibits basal and angiotensin II- and ACTHstimulated aldosterone release. These experiments provide important information concerning the role these cytokine may play in septic shock. The plasma concentration and probably adrenal concentration of IL-6, IL- I beta, and TNF are increased by endotoxin (LPS) during septic shock. Because angiotensin II is the primary regulator of aldosterone release under physiological conditions, these cytokines would decrease the adrenals release of aldosterone. Because aldosterone controls the salt and indirectly the water balance of the organism, these cytokines would lead to a decrease in salt and water retention. This decrease in total body water would potentiate the fall in blood pressure caused by the direct effects of these cytokines on the blood vessels (i.e., vaso-dilation).
These experiments were conducted as a portion of a much larger, on-going research project by my mentor, Dr. Allan Judd. I came away from this research with a more profound understanding of the endocrinimmunological states of our bodies and a greater appreciation for the methods, time, money, and effort required to conduct biomedical research.
