Attenuating tumor necrosis factor alpha does not ameliorate other cytokineand peroxidase products during sepsis

BACKGROUND: Recent trials utilizing single anticytokine agents have shown n o consistent survival benefit in improving the outcome of sepsis. Since an entire cascade of mediators contributes to the underlying pathophysiology, it is not surprising that monotherapy has proven unsuccessful. The purpose of this study was to measure the effects of attenuating tumor necrosis fact or (TNF)alpha early in sepsis, METHODS: Three groups of Sprague-Dawley rats were studied. All animals were infused with live Escherichia coli, with group I and group II rats additio nally receiving a matrix metalloproteinase inhibitor. Serum levels of TNF a lpha, interleukin (IL)-6, malondialdehyde (MDA), and lipid hydroperoxide (L OOH) were compared. RESULTS: TNF alpha showed a significant decrease, yet IL-6, MDA, and LOOH ( markers of sepsis) levels remained abnormally elevated. CONCLUSION: Despite significantly attenuating TNF alpha, the septic respons e continued. This supports the concept that in sepsis, monotherapy directed at attenuating a single cytokine cannot overcome the tissue-damaging effec ts of an entire cascade of mediators. Am J Surg. 1999;178: 556-559, (C) 199 9 by Excerpta Medica, Inc.