To reveal a pathway by which psychological/physical stresses influence host defense capability, responses to immobilization stress in mice were investigated, focusing on a multifunctional cytokine, interleukin-18 (IL-18). Immobilization stress induced interleukin-18 accumulation in plasma and in the adrenal gland. Inhibition on ACTH resulted in suppressed levels of IL-18 both in plasma and the adrenal gland. In hemi-adrenalectomized mice, plasma IL-18 levels after stress were lower than in sham-operated mice. This, together with the observation in stressed hemi-adrenalectomized mice that IL-6 levels in plasma were suppressed but up-regulated by recombinant IL-18, showed that the adrenal gland plays a crucial role in stress-related elevation of IL-6 in plasma via IL-18. Adrenal gland is highlighted as an organ connecting the psychological, endocrine, and immune systems. Controlling the secretion of IL-18 from the adrenal gland may serve as a possible preventative means against a stress-related disruption of host defenses.
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