Cross-protection by anti-core glycolipid antibodies: evidence from animal experiments

The ability of antibodies against the core glycolipid (CGL) of endotoxin to protect experimentally infected animals against death from Gram-negative sepsis is reviewed. The limitations and confounding factors inherent to animal models of sepsis are also briefly discussed. This review considers 30 studies in mice and 12 in other animal species that investigated protection against heterologous challenge by passive immunization with anti-CGL antibodies. In 28 (67%) of the reviewed studies antibodies were found to be protective, either prophylactically (n = 17) or therapeutically (n = 11). With the possible exception of the type of antibody preparation that was used (monoclonal versus polyclonal antibodies), none of the many differences in the experimental protocols were clearly correlated with success. Convincing proof is still lacking for any of the hypothetical mechanisms of protection by anti-CGL antibodies. Moreover, the evidence that protection by these antibodies is attributable to their anti-CGL specificity is poor. The available data raise serious questions about the validity of the concept underlying the search for broadly cross-protective antibodies raised against the core region of endotoxin. However, continuing research suggests that endotoxin still is a valid target in devising new adjunctive treatment strategies to improve the outcome of serious Gram-negative infections.