Mg. Schwacha et al., Resistance of macrophages to the suppressive effect of interleukin-10 following thermal injury, AM J P-CELL, 281(4), 2001, pp. C1180-C1187
The activation of a macrophage (M phi)-dependent proinflammatory cascade fo
llowing thermal injury plays an important role in the development of immuno
suppression and increased susceptibility to subsequent sepsis in burn patie
nts. In contrast, although interleukin (IL)-10, an antiinflammatory cytokin
e that can downregulate M phi activity, has also been implicated in postbur
n immune dysfunction, its role in the regulation of M phi function postburn
remains unclear. To study this, C57BL/6 female mice were subjected to a 25
% total body surface area third-degree scald burn, and splenic M phi s were
isolated 7 days later. Lipopolysaccharide (LPS)-stimulated IL-10, IL-6, tu
mor necrosis factor (TNF)-alpha, and nitric oxide (NO) production were sign
ificantly increased in the burn group compared with shams. Blockade of endo
genous IL-10 activity enhanced IL-6 and TNF-a release, but not NO release,
in both groups. The addition of exogenous IL-10 to the M phi cultures dose
dependently suppressed production of these inflammatory mediators in both g
roups. The timing of IL-10 addition to the cultures in relation to LPS stim
ulation, however, was critical. The suppressive effect of exogenous IL-10 w
as attenuated in both groups when the cells were exposed to IL-10 at 4-6 h
after LPS stimulation; however, M phis from injured mice were significantly
better able to maintain inflammatory mediator-productive capacity. The res
istance of M phis from injured mice to IL-10-mediated suppression correlate
d with decreased IL-10 receptor (IL-10R) expression and increased CD11b exp
ression. These findings suggest that M phis, following thermal injury, disp
lay resistance to suppression by IL-10 due in part to downregulation of IL-
10R expression.