Cs. Chung et al., Septic mucosal intraepithelial lymphoid immune suppression: Role for nitric oxide not interleukin-10 or transforming growth factor-beta, J TRAUMA, 48(5), 2000, pp. 807-812
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 ly
mphocytes (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 wheth
er IEL's IL-2/IFN-gamma production is suppressed and what mediates this dep
ression.
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 re
lease IL-2/IFN-gamma at 24 hours and that this decline is associated with i
ncreased 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 ce
lls. To further study whether NO was involved in this immune suppression, i
NOS knockout (iNOS -/-) were also subjected to the same procedure; however,
the depression in IL-2/IFN-gamma was not seen in iNOS -/- mice when compar
ed with background controls.
Conclusion: Our data indicate that IL-10, which affects splenic lymphoid re
sponse, may not be a keg mediator of IEL immune suppression and that the in
duction of NO may play a more significant role in gastrointestinal immune d
ysfunction seen in late sepsis.