title: Septic mucosal intraepithelial lymphoid immune suppression: role for nitric oxide not interleukin-10 or transforming growth factor-beta.
abstract: OBJECTIVE
  Recent studies indicate that sepsis induces a marked depression in the splenocyte immune response (as 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 C3H/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 IL-10 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.
  
  
  CONCLUSIONS
  Our data indicate that IL-10, which affects splenic lymphoid response, may not be a key 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.
authors.affiliation: Center for Surgical Research and Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence 02903, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Chung
authors.forename: G Y
authors.initials: GY
authors.lastname: Song
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: I H
authors.initials: IH
authors.lastname: Chaudry
authors.forename: A
authors.initials: A
authors.lastname: Ayala
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007108:Immune Tolerance / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism*; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism*; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000276:immunology*; D018805:Sepsis / Q000276:immunology*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma