Septic mucosal intraepithelial lymphoid immune suppression:: Role for nitric oxide not interleukin-10 or transforming growth factor-β

Objective: Recent studies indicate that sepsis induces a marked depression in the splenocyte immune response las illustrated by decreased interleukin [IL]-2 production, interferon [IFN]-gamma production, or both) in response to T-cell mitogen, However, it is not known whether a similar depression is evident in the phenotypically distinct, small intestine intraepithelial lymphocytes (IELs) or what regulates this process during sepsis, Because the maintenance of a competent mucosal immune response is thought to be central to the animal's ability to survive sepsis, we attempted to determine whether IEL's IL-2/IFN-gamma production is suppressed and what mediates this depression. Results: Our studies indicated that C3/HeN mice subjected to cecal ligation and puncture (CLP) exhibited a marked decline in the ability of IELs to release IL-2/IFN-gamma at 24 hours and that this decline is associated with increased secretion of IL-10 and nitric oxide (NO), To the extent that IL-10 accounted for this loss of IL-2/IFN-gamma release, we observed that LL-IO gene deficiency neither restored the IL-2/IFN-gamma release nor suppressed the increase in NO when compared with background control, C57BL/6J mouse cells. To further study whether NO was involved in this immune suppression, iNOS knockout (iNOS -/-) were also subjected to the same procedure; however, the depression in IL-2/IFN-gamma was not seen in iNOS -/- mice when compared with background controls. Conclusion: Our data indicate that IL-10, which affects splenic lymphoid response, may not be a keg mediator of IEL immune suppression and that the induction of NO may play a more significant role in gastrointestinal immune dysfunction seen in late sepsis.