Role of the cytokines in the hypothalamic-pituitary-adrenal and gonadal axes.

Cytokines are soluble mediators of immune function that also regulate several endocrine systems. Interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF alpha) each mediate certain aspects of inflammation. In addition, these agents regulate hormone secretion from and cellular proliferation within endocrine tissues. Thus, IL-1 and IL-6 each affect hormone release from anterior pituitary cells (e.g., growth hormone) and inhibit the proliferation of these cells. Cytokines are also localized within discrete nuclei of the hypothalamus (e.g., IL-1 in the paraventricular nucleus), where they may affect production of neuropeptides and biogenic amines (e.g., corticotropin-releasing hormone). Similarly, IL-1 and TNF alpha affect granulosa cell steroidogenesis and IL-6 production. Follicular atresia may either be augmented or inhibited by cytokines depending on their ability to regulate cellular apoptosis. Compartmentation of cytokines within adrenal tissue (e.g., IL-6 in the zona glomerulosa) allows localized effects of these factors on glucocorticoid secretion. Thus, cytokines affect via paracrine or autocrine pathways both hormone secretion from, and possibly cellular differentiation within, endocrine tissues.