Tohoku J. Exp. Med., 2002, 196 (4)

Effects of Interleukin-18 on Diaphragm Muscle Contraction on Rats

FUMIKO SASAKI, CHIYOHIKO SHINDOH, TOSHIFUMI NIWA,
TETSUYA OHTAKA
and YURIKO SHINDOH¹

Department of Medical Technology, College of Medical Sciences, Tohoku University, Sendai 980-8575, and
¹Department of Respiratory Medicine, Sendai City Medical Center, Sendai 983-0824

To evaluate the role of interleukin (IL)-18 in endotoxin-induced diaphragm muscle deterioration, we studied three treatment groups, namely, a saline+endotoxin group, an IL-18+endotoxin group and an IL-18 only group using Wistar rats. Five minutes after saline or IL-18 (0.25 mg) injection, E. coli endotoxin (30 mg/kg) was injected intraperitoneally. In the saline+endotoxin group, the force-frequency curves by ANOVA (p<0.01), twitch tension (TT) and slope during contraction time (TT/CT) were significantly lower at 4 hours than those at 0 hours due to endotoxin (p<0.01 and p<0.05, respectively) and nitric oxide (NO) production had increased at 4 hours as shown by NADPH diaphorase staining. In the IL-18+endotoxin group, the decrement of the force-frequency curves in a higher frequency range (50-120 Hz), and the decrements of TT and TT/CT observed at 4 hours in the saline+endotoxin group were significantly prevented, and NO production was blocked at 4 hours. In the IL-18 only group, the force-frequency curves did not change except for fatigability, and NO production did not occur. It is suggested that IL-18 itself naturally blocks NO production, even when endotoxin coexists, resulting in the prevention of deterioration of diaphragm muscle contraction by endotoxin.

Keywords—— cytokine; endotoxin; NADPH diaphorase; nitric oxide

© 2002 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2002, 196, 269-280

Address for reprints: Chiyohiko Shindoh, M.D., Prof., Department of Medical Technology, College of Medical Sciences, Tohoku University, 2-1 Seiryomachi, Aoba-ku, Sendai 980-8575, Japan.

e-mail: cshindoh@mail.cc.tohoku.ac.jp