Interleukins, signal transduction, and the immune system-mediated stress response.

摘要: Overwhelming evidence indicates that the administration of cytokines such as IL-1 alpha and beta, IL-6, TNF-1 stimulates one or more components HPA axis. The hypothesis driving this research is host infection tissue injury trigger synthesis release several act locally at sites trauma distally upon entering circulation. Available suggests primary source axis-acting circulating activated monocytes macrophages; therefore, a direct relationship should exist between appearance monokines in plasma subsequent pituitary-adrenocortical hormones well. Clarification physiological role mediators stress response will come from vivo studies which type, sequence appearance, duration elevation, quantification each monokine monitored along with ACTH glucocorticoids, following an appropriate immune challenge. In recent reports, investigators have administered bacterial-derived endotoxin LPS to stimulate events associated chronicled levels IL-1, TNF-alpha (37,56,57). human subjects, challenge enhanced by 1 hour, returned basal 4 hours (37), whereas, IL-6 activity increased 2 post-challenge baseline 6 (56). Thus, both these are implicated possible acute activators perhaps most revealing study date, mice indicated differential disappearance rate serum for regulation glucocorticoid feedback (57). Serum TNF was detected 45 minutes post-LPS, peaked control 3 hours. corticosterone concentrations rose rapidly over time course similar TNF. Even after concentration had conditions, remained maximally elevated, still significantly above 24-hour post-LPS. rapid return pre-LPS appeared be regulated negative feedback, because elevated least adrenalectomized hypophysectomized mice. LPS-induced were delayed compared TNF, hours, even 24 hours.(ABSTRACT TRUNCATED AT 400 WORDS)