Immunotherapy of sepsis: flawed concept or faulty implementation?

Gram-negative bacillary sepsis is a leading cause of death among patients hospitalized in intensive care units. While initial clinical studies with the passive administration of anti-endotoxin core-glycolipid (CGL) antibodies for the treatment and prophylaxis of sepsis showed promising results, subsequent studies failed to show a consistent benefit. There appears to be a good correlation between anti-CGL antibody levels at the onset of sepsis and maintenance of antibody levels during sepsis with outcome. Previous clinical studies may have failed because insufficient amounts of antibody were administered early in the course of sepsis. Unlike the case with anti-CGL antibodies, polyvalent, hyperimmune type-specific antibody preparations may prevent the development of infections; however, these antibodies also must be provided in adequate amounts and in close proximity to infection in order to provide a beneficial effect. These pharmacokinetic requirements may limit the utility of passive immunotherapy for the prophylaxis of sepsis. Active immunization of acutely traumatized patients or of rats subsequently rendered neutropenic with cyclophosphamide induced high antibody levels for extended periods of time. Since trauma and other conditions are associated with a Th(2) response, these conditions may favor antibody formation following active immunization. Active immunization with both anti-CGL and/or polyvalent-specific vaccines for the prophylaxis of sepsis with passive supplementation at the onset of sepsis is an approach that merits further investigation.