Considering immunomodulatory therapies in the septic patient: should apoptosis be a potential therapeutic target?

Treatment of sepsis and septic shock remains a clinical conundrum. Recent p rospective trials with anti-cytokine and anti-inflammatory therapies have s hown only modest clinical benefit. The successful treatment of the patient with sepsis syndrome will likely require multi-modal therapies aimed at sev eral of the immunological and physiological disturbances which are occurrin g simultaneously. Recent studies in experimental animals and critically ill patients have suggested that increased apoptosis of lymphoid organs and so me parenchymal tissues may contribute to the immune suppression, anergy and organ system dysfunction. Therapies aimed at inhibiting lymphoid cell apop tosis may contribute to improved outcome, and should be considered in the t reatment of hospitalized patients with sepsis syndromes. Although clinical trials with anti-apoptotic agents remain distant due in large part to techn ical difficulties associated with their administration and tissue targeting , inhibition of lymphocyte apoptosis may be an appropriate therapeutic targ et for the septic patient. (C) 2001 Elsevier Science B.V. All rights reserv ed.