IL-18; a cytokine translates a stress into medical science.
Psychological/physical stresses have been reported to exacerbate auto-immune and inflammatory diseases. To clarify a mechanism by which non-inflammatory stresses disrupt host defenses, responses to immobilization stress in mice were investigated, focusing on the role of a multifunctional cytokine, interleukin-18 (IL-18). In the adrenal cortex, the stress induced IL-18 precursor proteins (pro-IL-18) via ACTH and a superoxide-mediated caspase-1 activation pathway, resulting in conversion of pro-IL-18 to the mature form which was released into plasma. Inhibitors of caspase-1, reactive oxygen species and P38 MAPK prevented stress-induced accumulation of plasma IL-18. These inhibitors also blocked stress-induced IL-6 expression. This, together with the observation that IL-6 was not induced in stressed-IL-18 deficient mice, showed that IL-6 induction by stress is dependent on IL-18. In stressed organisms, IL-18 may influence pathological and physiological processes. Controlling the caspase-1 activating pathway to suppress IL-18 levels may provide preventative means against stress-related disruption of host defenses.
Sekiyama
Atsuo
A
Department of stress science, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan.
Ueda
Haruyasu
H
Kashiwamura
Shin-ichiro
S
Nishida
Kensei
K
Kawai
Kaori
K
Teshima-kondo
Shigetada
S
Rokutan
Kazuhito
K
Okamura
Haruki
H
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D061945:Caspase Inhibitors; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System; D015151:Immunoblotting; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008511:Medicine; D051379:Mice; D010913:Pituitary-Adrenal System; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D012149:Restraint, Physical / Q000502:physiology; D012586:Science; D013315:Stress, Psychological / Q000503:physiopathology*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D020382:Interleukin-18; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D013481:Superoxides; D000324:Adrenocorticotropic Hormone; D048051:p38 Mitogen-Activated Protein Kinases