A role of the adrenal gland in stress-induced up-regulation of cytokines in plasma

Abstract 

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.

Abbreviations: ACTH, adrenocorticotropic hormone, DMSO, dimethylsulfoxide, DPI, diphenyleneiodnium, ELISA, enzyme-linked immunosorbent assay, GCs, glucocorticoid, HPA, hypothalamus–pituitary–adrenal, IFN-γ, interferon-gamma, IL, interleukin, LPS, lipopolysaccharide, KO, knockout, mRNA, messenger ribonucleic acid, PBS, phosphate-buffered saline, SOD, superoxide-dismutase, Th, T helper, WT, wild-type

Keywords: Stress, Interleukin-18, Interleukin-6, Adrenal gland, Caspase-1, HPA axis