Regulation of pro-inflammatory and anti-inflammatory cytokine responses by Kupffer cells in endotoxin-enhanced reperfusion injury after total hepatic ischemia.
The effects of Kupffer cells on cytokine responses in endotoxin-enhanced reperfusion injury after total hepatic ischemia were investigated in this study. Male rats pretreated with either normal saline solution (NS group) or gadolinium chloride (GdCl(3)) to inhibit Kupffer cell function (GC group) were subjected to 60 min of hepatic ischemia. These animals received either normal saline solution or sublethal doses of endotoxin (1 mg/kg) at reperfusion. In the NS group, endotoxin administration induced an enhanced tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 production 1 h after reperfusion with a subsequent peak of macrophage inflammatory protein-2 (MIP-2) levels, which resulted in a 7-day survival rate of 30%. Despite endotoxin administration, GdCl(3) pretreatment significantly suppressed TNF-alpha and increased interleukin-10 production 1 h after reperfusion, which led to a decline in MIP-2 production and amelioration of functional and structural liver damage with a 7-day survival rate of 80%. Augmented pro-inflammatory and anti-inflammatory cytokine responses by Kupffer cells were associated with endotoxin-enhanced reperfusion injury after hepatic ischemia. Kupffer cell blockade has a potential to attenuate the insult via modulation of cytokine responses.
Second Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, 431-3192, Hamamatsu, Japan.
Yoshimitsu
Y
Kojima
Shohachi
S
Suzuki
Yasuo
Y
Tsuchiya
Hiroyuki
H
Konno
Satoshi
S
Baba
Satoshi
S
Nakamura
D000818:Animals; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D016207:Cytokines / Q000097:blood*; D004731:Endotoxins / Q000633:toxicity*; D036341:Intercellular Signaling Peptides and Proteins; D016753:Interleukin-10 / Q000097:blood; D007511:Ischemia / Q000097:blood / Q000276:immunology* / Q000473:pathology; D007700:Kinetics; D007728:Kupffer Cells / Q000276:immunology* / Q000473:pathology; D008102:Liver Circulation; D008297:Male; D015846:Monokines / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D015996:Survival Rate; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D054426:Chemokine CXCL2; D019743:Chemokines, CXC; C513296:Cxcl2 protein, rat; D016207:Cytokines; D004731:Endotoxins; D036341:Intercellular Signaling Peptides and Proteins; D015846:Monokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10