Mechanism of the beneficial effects of pentoxifylline on hepatocellular function after trauma hemorrhage and resuscitation.
BACKGROUND
The purpose of this study was to determine whether pentoxifylline administration restores the depressed hepatocellular function after trauma hemorrhage and crystalloid resuscitation and, if so, whether this is the result of the down-regulation of inflammatory cytokines, tumor necrosis factor (TNF) and interleukin-6 (IL-6).


METHODS
After laparotomy rats were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of maximum shed blood volume was returned in the form of Ringer's lactate. They were then resuscitated with Ringer's lactate to four times the shed blood volume. Pentoxifylline (50 mg/kg body weight) or saline solution was infused intravenously for 95 minutes during and after resuscitation. One and a half hours and 4 hours after resuscitation, hepatocellular function (maximal velocity [Vmax] and the efficiency of the active transport [Km] of indocyanine green clearance) and plasma. TNF and IL-6 levels were determined with in vivo hemoreflectometer and cellular assays, respectively.


RESULTS
Circulating TNF and IL-6 levels increased significantly after hemorrhage and resuscitation. Pentoxifylline treatment, however, markedly decreased the levels of these cytokines, and the values were similar to those of sham rats. The decreased Vmax and Km values were also restored by pentoxifylline treatment. Moreover, there was a significant correlation between Vmax and TNF or IL-6 levels.


CONCLUSIONS
The down-regulation of inflammatory cytokines by pentoxifylline may be the mechanism by which this agent restores the depressed hepatocellular function after trauma hemorrhage and resuscitation.
Wang
P
P
Department of Surgery, Michigan State University, East Lansing 48824-1315.
Ba
Z F
ZF
Morrison
M H
MH
Ayala
A
A
Chaudry
I H
IH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006470:Hemorrhage / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012151:Resuscitation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014947:Wounds and Injuries / Q000503:physiopathology*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline