Role of immunomodulator therapy in sepsis

Endotoxin is released from the cell walls of gram-negative bacteria and causes severe systemic effects due to the release of cytokines. Monoclonal antibodies directed at endotoxin may be promising adjuncts to the standard therapeutic interventions of antibiotics and supportive measures used to treat patients with gram-negative sepsis. Monoclonal antibodies interfere with the bacteria's ability to trigger an unfavorable response. In recent clinical trials, two immunoglobulin M monoclonal antibodies have improved survival in certain small patient subgroups, although neither drug improved overall mortality in all septic patients treated. E5 murine monoclonal antibody reduced mortality in patients with gram-negative sepsis who were not in refractory shock. HA-1A human monoclonal antibody reduced mortality in patients with gram-negative infections who were bacteremic or in shock. The statistical significance and clinical importance of these benefits is not yet known. Results of these clinical trials are reviewed.