The Therapeutic Effect of Anti - inflammatory Agents on the Lethal Effect of Toxemia Evoked by Vibrio vulnificus Cytolysin

Park, Jae Hoon; Park, Seok Don

Abstract

BACKGROUND: Many pathophysiological derangements associated with Vibrio vulnificus sepsis result from the release of toxins and enzymes into the circulation. Its effects are mediated via complex interaction of many endogenous inflammatory mediators such as tumor necrosis factor (TNF)-a, bradykinin, histamine, and nitric oxide.
OBJECTIVE
The purpose of this study is to evaluate the effects of antinflammatory agents (antiTNF-a, antihistamine, steroid, antibradykinin, and nitric oxide synthase inhibitor) on the lethal effect of toxemia evoked by Vibrio vulnificus cytolysin.
METHODS
The study consisted of 4 groups of mice. Control mice received a bolus intravenous infusion of cytolysin or anti-inflammatory modalities. Drug administration was designed in accordance with the time of cytokine release(TNF-a, IL-6,8) and scored for survival rate at 72 hours after last infusion. Group I mice(early treatment group) received intraperitoneal infusions of each anti-inflammatory modalities at 1 hour after cytolysin infusion. Group II mice(delayed treatment group) received each anti-inflammatory agent treatment at 2, 4, 12 hours after the cytolysin infusion. Group III(early combined treatment group) received intraperitoneal infusions of combined anti-inflamrnatory agents at 1 hour after cytolysin infusion. Group IV(delayed combined treatment. group) received combined anti-inflammatory agents at 2, 4, 12 hours after cytolysin infusion. Autopsies were performed in dead mice after cytolysin infusion for gross and microscopic studies.
RESULTS
In the control group, all mice infused with cytolysin died and all mice treated with antiinflammatory agents survived. Survival rate of group I showed 75% in aprotinin, 88% in prednisolone, 75% in N-methyl-L-arginine, 88% in pentoxifylline, 100% in hydroxyzine HC1. Group II showed 40%, 40%, 60 %, 60%, 80% in order of the agents, respectively, Mean survival rate of each agents showed 85 % in group I and 56% in group II. Results of treatment revealed 100% survival in group III and 80% in group IV. In evaluation of effectiveness of therapeutic modalities, all died in the no therapeutic group and a 76.9% survaal rate in the therapeutic group was noted. The gross and microscopic finding showed similar findings to sepsis.
CONCLUSION
These results suggest that inhibitors of endogenous inflammatory mediators may improve the survival rate in th treatment of septic shock caused by Vibrio vulnificus and ot,her grarn negative bacilli. Also this study support the proposal that early treatment in V, vulnificus septicemia is essential for reduced mortality.