Zoe A. Gillis

Effect of a human immunoglobulin preparation for intravenous use in a rabbit model of meningococcal endotoxin-induced shock

Background and Methods:Endotoxin shock is mediated by various cytokines, including tumor necrosis factor. Treatment of patients with iv immunoglobulin has been shown to reduce the concentration of circulating cytokines. The purpose of this study was to determine the protective effects of immunoglobulin for iv use on meningococcal endotoxin-induced shock in a rabbit model. Experimental animals were challenged with iv meningococcal endotoxin (lipo-oligosaccharide) 10 μg/kg, and treated with either a 2-hr iv immunoglobulin infusion (400 mg/kg) or a similar saline infusion that was initiated 30 mins before endotoxin challenge. Control animals were challenged with saline alone. Results:Compared with untreated control animals, pulse rate increased (p < .007) and mean arterial pressure and serum bicarbonate concentrations decreased (p < .02) in both experimental groups, but did not differ between immunoglobulin-treated and saline-treated animals (p > .05) at any time after the endotoxin challenge. Geometric mean serum endotoxin concentrations were significantly (p < .03) lower in the immunoglobulin-treated animals at 60,120, 180, 240, 300, and 360 mins after the endotoxin challenge. The geometric mean serum tumor necrosis factor level at 1 hr after the endotoxin challenge in the immunoglobulin-treated experimental animals was lower than in saline-treated animals (5.53 vs. 8.47 tumor necrosis factor enzyme-linked immunosorbent assay U/mL), but not significantly so (p > .05). Mortality rate was similar in both experimental groups; eight (67%) of 12 saline-treated experimental rabbits and seven (70%) often immunoglobulin-treated rabbits died. All untreated control animals survived 24 hrs. Conclusions:In this model of circulatory shock in rabbits, iv immunoglobulin: a) does not significantly alter the physiologic responses to endotoxin challenge; b) significantly reduces endotoxin concentrations; c) reduces tumor necrosis factor concentrations, but not significantly; and d) does not improve survival rate.