Is gut the major source of proinflammatory cytokine release during polymicrobial sepsis?

Although studies have shown that the gut is capable of being a cytokine-pro ducing organ and that the proinflammatory cytokines TNF-alpha, IL-1 beta, a nd IL-6 are upregulated following the onset of sepsis, it remains unknown w hether the gut is indeed the major source of the increased cytokine product ion under such conditions. To determine this, male rats were subjected to c ecal ligation and puncture (CLP, a model of polymicrobial sepsis) or sham o peration followed by the administration of normal saline solution subcutane ously (i.e., fluid resuscitation). Systemic and portal blood samples were t aken simultaneously at 2, 5, 10, or 20 h after CLP or sham operation. Plasm a levels of TNF-alpha, IL-1 beta, and IL-6 were determined using an enzyme- linked immunosorbent assay. In additional animals, the small intestine was harvested at 10 h after CLP or sham operation and examined for TNF-alpha, I L-1 beta, and IL-6 gene expression by RT-PCR. The results indicate that the levels of TNF-alpha, IL-1 beta, and IL-6 in both systemic and portal blood samples were significantly elevated during sepsis with the exception that the increase in IL-1 beta was not significant at 2 h after CLP. However, th ere were no significant differences in the levels of those proinflammatory cytokines between systemic and portal blood at any points after the onset o f sepsis. Moreover, there were no significant alterations in the proinflamm atory cytokine gene expression in the small intestine at 10 h after CLP. Si nce the levels of TNF-alpha, IL-1 beta, and IL-6 were not significantly inc reased in portal blood as compared to systemic blood and since there was no upregulation of gene expression for these cytokines, it appears that organ s other than the gut are responsible for the upregulated proinflammatory cy tokines during polymicrobial sepsis. (C) 1999 Elsevier Science B.V. All rig hts reserved.