Interleukin-12 prevents diaphragm muscle deterioration in a septic animal model

The effects of an intravenous injection of Interleukin-12 (IL-12) after endotoxin administration and without endotoxin administration on diaphragm muscle were studied using Wistar rats. Three treatment groups, namely a control (Saline+endotoxin) group, an IL-12+endotoxin group and an IL-12 only group were studied. E. coli endotoxin (30 mg/kg) was injected intraperitoneally 5 min after Saline or IL-12 (0.25 microg) injection. In the control group, the force-frequency curves, twitch tension (TT) and slope during contraction time (TT/CT) were significantly lower at 4 h than those at 0 h due to endotoxin (P<0.001, P<0.01 and P<0.01, respectively), and NO production was increased at 4 h as shown by NADPH diaphorase staining. In the IL-12+endotoxin group, the decrement of the force-frequency curves, TT and TT/CT induced by endotoxin at 4 h were significantly prevented compared with those of the control group (P<0.001, P<0.05 and P<0.05, respectively), and NO production was blocked at 4 h. In the IL-12 only group, the force-frequency curves were decreased in the range of high frequency and IL-12 resulted in NO production. Furthermore, the positive muscle fibers detected by NADPH diaphorase staining were classified as type I and IIa muscle fibers by ATPase staining in the control and IL-12 only groups. It is concluded that IL-12 prevents the deterioration of diaphragm muscle contraction induced by endotoxin by reducing NO production in type I and IIa muscle fibers. These results suggest that IL-12 and endotoxin may interfere with each other.