Immunotherapy of sepsis: flawed concept or faulty implementation?

Gram-negative bacillary sepsis is a leading cause of death among patients h ospitalized in intensive care units. While initial clinical studies with th e passive administration of anti-endotoxin core-glycolipid (CGL) antibodies for the treatment and prophylaxis of sepsis showed promising results, subs equent studies failed to show a consistent benefit. There appears to be a g ood correlation between anti-CGL antibody levels at the onset of sepsis and maintenance of antibody levels during sepsis with outcome. Previous clinic al studies may have failed because insufficient amounts of antibody were ad ministered early in the course of sepsis. Unlike the case with anti-CGL ant ibodies, polyvalent, hyperimmune type-specific antibody preparations may pr event 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 limi t the utility of passive immunotherapy for the prophylaxis of sepsis. Activ e immunization of acutely traumatized patients or of rats subsequently rend ered neutropenic with cyclophosphamide induced high antibody levels for ext ended periods of time. Since trauma and other conditions are associated wit h a Th-2 response, these conditions may favor antibody formation following active immunization. Active immunization with both anti-CGL and/or polyvale nt-specific vaccines for the prophylaxis of sepsis with passive supplementa tion at the onset of sepsis is an approach that merits further investigatio n. (C) 1999 Elsevier Science Ltd. All rights reserved.