IL-18 mediates the formation of stress-induced, histamine-dependent gastric lesions.
A role of IL-18 in the induction of gastric lesions by water immersion and restraint stress (WRS) was investigated. When wild-type BALB/c mice were exposed to WRS, levels of IL-18 in the serum and stomach increased rapidly with the development of acute gastric lesions. In IL-18-deficient mice [IL-18 knockout (KO) mice] similarly exposed to WRS, no gastric lesions were observed, but the administration of IL-18 before exposure to WRS resulted in the induction of WRS-induced gastric lesions. WRS enhanced gastric histidine decarboxylase (HDC) activity with concomitant increases in gastric histamine content. In IL-18 KO mice, the WRS-induced elevation of gastric HDC activity and histamine levels was much less than that in wild-type mice, but it was augmented by prior administration of IL-18. Treatment of wild-type mice with cimetidine, a histamine H2 receptor antagonist, inhibited the formation of WRS-induced gastric lesions with no effect on the induction of gastric IL-18 by WRS. Levels of corticosterone, one of the stress indicators, were lower in IL-18 KO mice than in wild-type mice. The glucocorticoid receptor antagonist mifepristone had no effect on gastric IL-18 and histamine levels but aggravated the stress-induced gastric lesions, indicating that corticosterone was not involved in the IL-18-mediated formation of stress-induced gastric lesions. These results indicate that IL-18 is involved in the induction of gastric lesions by WRS through augmentation of HDC activity and production of histamine in the stomach.
Seino
Hitomi
H
Department of Neuropsychiatry, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Hyogo, Japan.
Ueda
Haruyasu
H
Kokai
Masahiro
M
Tsuji
Noriko M
NM
Kashiwamura
Shinichiro
S
Morita
Yoshio
Y
Okamura
Haruki
H
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D006632:Histamine / Q000502:physiology*; D006636:Histamine Release / Q000502:physiology*; D020382:Interleukin-18 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012149:Restraint, Physical; D013272:Stomach Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D013315:Stress, Psychological / Q000473:pathology / Q000503:physiopathology*
D020382:Interleukin-18; D006632:Histamine