Tumor necrosis factor-alpha hyporesponsiveness of rat intestinal mononuclear cells and whole portal venous blood after hemorrhagic shock.

OBJECTIVE

To determine the effect of hemorrhagic shock on spontaneous and endotoxin-induced cytokine release from intestinal mononuclear cells compared with whole portal venous blood and splenic macrophages.

DESIGN

Random assignment to either unmanipulated control group, sham operation group, or hemorrhagic shock group.

SETTING

University animal laboratory.

SUBJECTS

Male Wistar rats, weighing between 300 and 350 g.

INTERVENTIONS

Rats were bled to 30 mm Hg for 30 mins by withdrawal/reinfusion of shed blood and Ringer's lactate equivalent to the shed blood volume.

MEASUREMENTS

Rats were killed immediately, 4 hrs, or 24 hrs after reperfusion. Portal venous blood, splenic macrophages, and small bowel mononuclear cells were obtained and spontaneous (unstimulated) and endotoxin-induced supernatant tumor necrosis factor (TNF)-alpha (WEHI 164 subclone 13) and interleukin (IL)-6 (B 13-29 clone 9) release was measured by bioassay.

MAIN RESULTS

Increased endotoxin-induced TNF release from gut mononuclear cells and portal venous blood was suppressed 4 and 24 hrs after reperfusion compared with sham operated animals (p < .05). TNF release from splenic macrophages could be significantly increased (p < .05) by addition of endotoxin in all groups with no difference between control, sham, and shock animals. In shock animals, endotoxin-stimulated IL-6 release was significantly greater (p < .05) than control and sham operated rats 4 hrs after reperfusion in portal blood and from splenic macrophages. In contrast to splenic macrophages, gut mononuclear cells and portal venous blood demonstrated high spontaneous IL-6 concentrations without further stimulation by endotoxin.

CONCLUSIONS

Hemorrhagic shock induced a hyporesponsiveness from gut mononuclear cells and whole portal venous blood 4 and 24 hrs after reperfusion. Spontaneous and endotoxin-induced stimulation of IL-6 indicates a different modulation of cytokines in gut, portal vein and spleen. The differences of gut mononuclear cells and portal blood compared with the splenic macrophages indicate a compartmentalized cytokine response.