Although Interleukin-6 (IL-6) plays an important role in the pathophys
iology 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 rel
ease following trauma-hemorrhage and resuscitation. KC numbers were si
gnificantly (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 maint
ained at a mean arterial pressure of 40 mmHg until 40% of the shed blo
od volume was returned as Ringer's lactate, and then resuscitated with
Ringer's lactate (four times shed blood volume over 1 h). Results ind
icate 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 pressu
re, heart rate, cardiac output, stroke volume, and hematocrit were red
uced to a similar extent in both the KC(+) and KC(-) hemorrhage groups
. KC reduction did, however, significantly reduce plasma IL-6 concentr
ation (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.