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Am J Physiol Regul Integr Comp Physiol 267: R446-R454, 1994;
0363-6119/94 $5.00
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AJP - Regulatory, Integrative and Comparative Physiology, Vol 267, Issue 2 446-R454, Copyright © 1994 by American Physiological Society


ARTICLES

TNF-alpha and IL-6 expression in perfused rat liver after intraportal candidemia vs. E. coli or S. aureus bacteremia

G. M. Matuschak, C. Munoz, N. A. Epperly, R. S. Britton, D. Walsh, D. R. Schilly, T. L. Tredway, T. A. Khan, B. R. Bacon and A. J. Lechner
Department of Internal Medicine, Saint Louis University Health Sciences Center, Missouri.

We tested the hypothesis that regulation of tumor necrosis factor-alpha (TNF-alpha) and IL-6 by the liver differs after intraportal challenge with Candida albicans spp. vs. gram-negative or gram-positive bacteria, independent of microbial clearance kinetics or hepatic O2 consumption (VO2). Buffer-perfused rat livers were infected with equivalent inocula (10(9) colony-forming units) of viable Escherichia coli serotype 055:B5 (EC), exotoxin C-producing Staphylococcus aureus (SA), or two strains of yeast phase C. albicans (CA-1 and CA-2). Microbial clearance and circulating cytokine levels were assessed over 180 min while monitoring VO2 and functional parameters, after which organ-based microbial killing, cell-associated TNF-alpha, and cytokine mRNA levels were determined. Compared with saline controls (normal saline solution; NSS), circulating and cell-associated TNF-alpha and TNF-alpha transcripts minimally increased after CA. In contrast, large increases in perfusate TNF-alpha occurred after EC, peaking at 180 min [135 +/- 32 U/ml (mean + SE)], concomitant with rises in cell-associated cytokine and TNF-alpha transcripts (P < 0.01 vs. NSS). Circulating TNF-alpha also rose after SA but neither cell-associated nor mRNA levels exceeded NSS values. There were no pathogen-specific differences in microbial clearance or VO2. IL-6 gene expression paralleled that for TNF-alpha, but IL-6 bioactivity in perfusates was inhibited by TNF-alpha-dependent and -independent mechanisms. We conclude that hepatic TNF-alpha and IL-6 expression are differentially regulated after taxonomically diverse microbial challenges, with E. coli eliciting the strongest and Candida spp. the weakest stimulatory responses.





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