Sepsis induces an early increased spontaneous release of hepatocellular stimulatory factor (interleukin-6) by Kupffer cells in both endotoxin tolerant and intolerant mice.
Previous studies have shown that hepatocellular function is significantly depressed early during sepsis and that this is associated with a marked increase in the circulating levels of the hepatocellular stimulatory factor (IL-6). It remains unknown, however, whether or not Kupffer cells (KC) are activated during sepsis and whether these cells are the major contributors to the increased circulating levels of this cytokine. The objectives of this study were, therefore, to determine whether or not during sepsis: (1) KC are stimulated in vivo to release IL-6, as compared to other cytokines; (2) KC differ from splenic macrophages (SM phi) in their ability to release cytokines; and (3) there is a difference in macrophage (M phi) cytokine release between endotoxin (ET)-tolerant (C3H/HeJ) and ET-intolerant (C3H/HeN) mice. To assess this, KC and SM phi were harvested at 1 or 24 hr from mice which had been subjected to polymicrobial sepsis by cecal ligation and puncture (CLP) or sham-operation. Following depletion of the nonadherent cells, KC and SM phi cultures were incubated for 24 hr in the presence or absence of 10 micrograms of ET/ml, and the levels of interleukin (IL)-1, IL-6, and TNF release were determined by bioassays. Sepsis induced an early (at 1 hr) in vivo stimulation of KC but not SM phi IL-6 release, irrespective of ET-tolerance/intolerance. However, the release of IL-1 or TNF was not markedly different for either CLP or sham KC.(ABSTRACT TRUNCATED AT 250 WORDS)
Ayala
A
A
Department of Surgery, Michigan State University, East Lansing 48824.
Perrin
M M
MM
Wang
P
P
Chaudry
I H
IH
D000818:Animals; D004361:Drug Tolerance; D004731:Endotoxins / Q000633:toxicity*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D007728:Kupffer Cells / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018805:Sepsis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha