Production of tumor necrosis factor-alpha, interleukin-1 and interleukin-6 in the perfused rat liver.
The kinetics of the production and release of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6) were investigated in the perfused rat liver and in primary cultures of Kupffer cells after stimulation with lipopolysaccharide (LPS). A small and transient accumulation of TNF-alpha could be detected immunohistochemically and by cytotoxicity assay in the intracellular space about 1 h after addition of LPS to the cultured cells. TNF-alpha release in the perfused liver followed similar kinetics as those found in the serum of LPS-treated rats and in primary cultures of rat Kupffer cells. The cytotoxic TNF-alpha activity of the perfusate attained its maximum (11.5 +/- 2.6 U/ml) 90 min after LPS stimulation and remained nearly constant for further 150 min. 2 microM dexamethasone reduced the production of TNF-alpha by 10 g of liver during 240 min from 46 to 16 x 10(3) units. The production of IL-1 and IL-6 by 10 g of liver during the initial 240 min was 3 and 530 x 10(3) IU, respectively. The maximal concentrations of IL-1 (1.4 +/- 0.7 IU/ml) and IL-6 (157 +/- 60 IU/ml) were found 240 min after LPS addition. The production of IL-1 was totally suppressed by 2 microM dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)
Tran-Thi
T A
TA
Biochemisches Institut, Albert-Ludwigs-Universitat, Freiburg, Germany.
Weinhold
L
L
Weinstock
C
C
Hoffmann
R
R
Schulze-Specking
A
A
Northoff
H
H
Decker
K
K
D000818:Animals; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D007728:Kupffer Cells / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000276:immunology*; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha