Role of Kupffer cells in interleukin-6 release following trauma-hemorrhage and resuscitation.
Although interleukin-6 (IL-6) plays an important role in the pathophysiology of trauma-hemorrhage and resuscitation, the cellular origin of this inflammatory cytokine remains unknown. This study was undertaken to determine whether Kupffer cells (KC) are a major source of IL-6 release following trauma-hemorrhage and resuscitation. KC numbers were significantly (p < .05) reduced in vivo with gadolinium chloride (GdCl3; 10 mg/kg IV). KC-reduced (KC(-)) and KC-normal (saline-treated; KC(+)) rats underwent laparotomy (i.e., trauma-induced), followed by either sham operation or hemorrhage. Hemorrhaged rats were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of the shed blood volume was returned as Ringer's lactate, and then resuscitated with Ringer's lactate (four times shed blood volume over 1 h). Results indicate that KC reduction per se had no effect on any measured parameter at any time. At 0.5 and 2.0 h postresuscitation, mean arterial pressure, heart rate, cardiac output, stroke volume, and hematocrit were reduced to a similar extent in both the KC(+) and KC(-) hemorrhage groups. KC reduction did, however, significantly reduce plasma IL-6 concentration (means +/- S.E.; U/ml) at both 0.5 h (KC(+) = 709 +/- 391 vs. KC(-) = 159 +/- 5) and at 2.0 h (KC(+) = 527 +/- 394 vs. KC(-) = 83 +/- 20) postresuscitation. In conclusion, this study demonstrates that KC are a major source of in vivo IL-6 release following trauma-hemorrhage and resuscitation.
O'Neill
P J
PJ
Department of Surgery, Michigan State University, East Lansing 48824-1315, USA.
Ayala
A
A
Wang
P
P
Ba
Z F
ZF
Morrison
M H
MH
Schultze
A E
AE
Reich
S S
SS
Chaudry
I H
IH
D000818:Animals; D002319:Cardiovascular System / Q000503:physiopathology; D002452:Cell Count; D005682:Gadolinium / Q000494:pharmacology; D006470:Hemorrhage / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism*; D007728:Kupffer Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D014947:Wounds and Injuries / Q000150:complications / Q000503:physiopathology* / Q000628:therapy
D015850:Interleukin-6; D005682:Gadolinium; C038958:gadolinium chloride