Infiltrating immune cells produce superoxide whose damage recruits more immune cells leading to the vicious cycle associated with many inflammatory diseases, including Crohn's disease, irritable bowel disease, and ulcerative colitis. Administration of superoxide dismutase (SOD) to convert superoxide to hydrogen peroxide shows no efficacy in clinical trials, although the phosphatidylcholine-conjugated (PC) or lecithinized SOD does, presumably due to enhanced stability and immune cell membrane targeting. In this issue, Ishihara et al., provide a mechanistic rationale for the bell-shaped dose response seen with PC-SOD, and the authors suggest improved dosing regimens. A combination of in vitro studies and in vivo spin-trapping of superoxide shows that moderate intravenous and oral doses of PC-SOD reduce superoxide levels, whereas higher doses lead to excessive accumulation of hydrogen peroxide. The suggestion that less frequent, moderate doses will be efficacious offers hope for alternative treatment of irritable bowel disease, ulcerative colitis, and perhaps other inflammatory conditions.
See article at J Pharmacol Exp Ther 2009, 328:152–164.
- The American Society for Pharmacology and Experimental Therapeutics