Immunotherapy of gram-negative bacterial sepsis: enhanced survival in a guinea pig model by use of rabbit antiserum to Escherichia coli J5.

A rough mutant of Escherichia coli (J5), which expresses a core lipopolysaccharide antigen common to gram-negative organisms on its cell surface, was used to immunize rabbits. Passively transferred anti-E. coli J5 rabbit antiserum (anti-J5 RS), normal rabbit serum (NRS), and saline were compared in a guinea pig model of intravenous gram-negative sepsis, with E. coli 0111:B4 and Pseudomonas aeruginosa as challenge organisms. Physiologic monitoring demonstrated a consistent pattern associated with gram-negative sepsis in this model: hypothermia, hypotension, bradycardia, a fall in white blood cell count and platelet count, and persistence of challenge organisms within the circulation. Pretreatment with anti-J5 RS prevented hypothermia and the fall in platelet count while augmenting bacterial clearance. Survival was markedly enhanced by anti-J5 RS, but not by NRS or saline. Concomitant heparin pretreatment was thought to be a significant factor in demonstrating the protective effect in this model. Parallel in vitro cross-reactivity measured by an enzyme-linked immunosorbent assay and an opsonization assay demonstrated that anti-J5 RS extensively cross-reacted with a variety of gram-negative bacilli. Demonstration of enhanced opsonization by anti-J5 RS of gram-negative organisms was thus well correlated with enhanced systemic clearance of bacteria and improved survival subsequent to intravenous bacterial challenge.