Administration ofAnti-TNFAntibody Improves LeftVentricular Functionin SepticShockPatients* Resultsof a PilotStudy

In this pilot study, murine monoclonal anti-TNF antibody (2 mg/kg) was administered to ten patients within 24 h of septic shock which persisted after initial resuscitation with intravenous fluids and adrenergic agents. This treatment resulted in a reduction in heart rate (from 122 ±10 to 113± 10 beats per minute at 4 h, pscientific progress, septic shock re mains a highly fatal disease so that new thera peutic options must be sought. Recent experimental and clinical studies have implicated TNF (TNF-alpha 01' cachectin), a macrophage-derived cytokine, as a potentially important mediator of septic shock. This has been based Ofl three observations. First, TNF blood levels in severely septic patients have been related to the severity of the acute disease' and the likelihood of death,2'7 Second, the administration of TNF in animals reproduces the hemodynamic, meta bolic and pathologic findings associated with endotoxic shock.s9 Therapeutic infusion of TNF in cancer pa tients also can result iii fever, tachycardia, hypotension and increased energy substrate 0 Third, the administration of anti—TNFantil)odies in animals can counteract the deleterious effects of endotoxin”-'2 or improve survival from Gram-negative sepsis.