Attenuating tumor necrosis factor alpha does not ameliorate other cytokine and peroxidase products during sepsis.
BACKGROUND
Recent trials utilizing single anticytokine agents have shown no 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 factor (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 additionally receiving a matrix metalloproteinase inhibitor. Serum levels of TNFalpha, interleukin (IL)-6, malondialdehyde (MDA), and lipid hydroperoxide (LOOH) were compared.


RESULTS
TNFalpha showed a significant decrease, yet IL-6, MDA, and LOOH (markers of sepsis) levels remained abnormally elevated.


CONCLUSIONS
Despite significantly attenuating TNFalpha, the septic response continued. This supports the concept that in sepsis, monotherapy directed at attenuating a single cytokine cannot overcome the tissue-damaging effects of an entire cascade of mediators.
Mazolewski
P J
PJ
Department of Surgery, University of Nevada School of Medicine, Las Vegas 89102, USA.
Barber
A
A
Williams
S
S
Simoni
J
J
Davis
S
S
Shires
G T
GT
D000818:Animals; D001593:Benzyl Compounds; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004338:Drug Combinations; D004927:Escherichia coli Infections / Q000378:metabolism / Q000517:prevention & control*; D008054:Lipid Peroxides / Q000494:pharmacology*; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D010431:Pentoxifylline / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013386:Succinates; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
C101468:BB 1101; D001593:Benzyl Compounds; D016207:Cytokines; D004338:Drug Combinations; D008054:Lipid Peroxides; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013386:Succinates; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D010431:Pentoxifylline