Effect of Erythromycin on Biological Activities Induced byClostridium perfringensα-Toxin

Abstract

Clostridium perfringens ␣-toxin, an important agent of gas gangrene with inflammatory myopathies, possesses lethal, hemolytic, and necrotic activities. Here, we show that ␣-toxininduced lethality in mice was inhibited by i.v. preadministration of erythromycin (ERM

Effect of Macrolide Antibiotics on Biological Activities Induced by Clostridium perfringens Alpha-Toxin

“…These results show that the 14-ring and the 15-ring macrolides have inhibitory effects on the lethality of alpha-toxin, but the 16-ring macrolides do not. The result coincided with that reported previously (Oda et al 2008). …”

“…Bunderen et al also found that the toxin-induced hemolysis is an additional prominent factor in the pathogenesis of septicemia caused by C. perfringens (van Bunderen et al 2010). We have reported the relationship between the toxin-induced hemolysis and activation of phospholipid metabolism via pertussis toxin-sensitive GTP-binding protein (Gi) (Sakurai, Ochi and Tanaka 1994, Ochi et al 1996, Ochi et al 2004, Oda et al 2008. Intravenous injection of alpha-toxin in mice resulted in massive intravascular hemolysis (Sugahara andOsaka 1970, Kreidl, Green andWren 2002).…”

“…However, little is known about the inhibitory mechanism of the antibiotics. Recently we revealed that macrolides prevent the toxininduced death, production of O 2 -, and release of TNF-α in neutrophils through inactivation of TrkA (Oda et al 2008). ERM and AZM inhibited the toxin-induced phosphorylation of TrkA under conditions in which the toxin inhibits biological activities; production of O 2 -and release of TNF-α (Fig.…”

“…Stevens et al reported that alpha-toxin may cause shock indirectly by stimulating the release of endogenous mediators Stevens 1996, Stevens 2000). We found that the intravenous injection of alpha-toxin in mice resulted in the release of various cytokines (Oda et al 2008). Cytokines are immunoregulatory peptides with a strong inflammatory action, mediating the immune/metabolic response to an external noxious stimulus and later the transition from septicemia to septic shock, multiple organ dysfunction syndromes, and/or multiple organ failure (Tracey et al 1987, Riedemann, Guo and Ward 2003, Dinarello 2004.…”

Gas-forming liver abscess associated with rapid hemolysis in a diabetic patient

“…However, penicillin and cephalosporin do not have such activity. Oda et al [49] have reported that erythromycin pretreatment reduces the release of TNF-α from activated neutrophils and suppresses hemolysis.…”