TNF-alpha and IL-6 expression in perfused rat liver after intraportal candidemia vs. E. coli or S. aureus bacteremia.
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.
Matuschak
G M
GM
Department of Internal Medicine, Saint Louis University Health Sciences Center, Missouri.
Munoz
C
C
Epperly
N A
NA
Britton
R S
RS
Walsh
D
D
Schilly
D R
DR
Tredway
T L
TL
Khan
T A
TA
Bacon
B R
BR
Lechner
A J
AJ
D000818:Animals; D016470:Bacteremia / Q000378:metabolism*; D001769:Blood / Q000382:microbiology*; D002175:Candida / Q000302:isolation & purification*; D004927:Escherichia coli Infections / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D008297:Male; D010101:Oxygen Consumption; D010477:Perfusion; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000378:metabolism; D013211:Staphylococcus aureus; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha