Dh. Libraty et al., INTERFERON-GAMMA DIFFERENTIALLY REGULATES INTERLEUKIN-12 AND INTERLEUKIN-10 PRODUCTION IN LEPROSY, The Journal of clinical investigation, 99(2), 1997, pp. 336-341
The ability of monocytes to influence the nature of the T cell respons
e to microbial pathogens is mediated in part by the release of cytokin
es. Of particular importance is the release of IL-12 and IL-10 by cell
s of the monocyte/macrophage lineage upon encountering the infectious
agent. IL-12 promotes cell mediated immunity (CMI) to intracellular pa
thogens by augmenting T-helper type I responses, whereas IL-10 downreg
ulates these responses. The ability of IFN-gamma to modulate the balan
ce between IL-12 and IL-10 production was examined by studying leprosy
as a model. In response to Mycobacterium leprae stimulation, IFN-gamm
a differentially regulated IL-12 and IL-10 production resulting in upr
egulation of IL-12 release and downregulation of IL-10 release. Furthe
rmore, we determined that the mechanism by which IFN-gamma downregulat
es IL-10 was through the induction of IL-12. The data suggest a model
of lymphocyte-monocyte interaction whereby the relative presence or ab
sence of IFN-gamma in the local microenvironment is a key determinant
of the type of monocyte cytokine response, and hence the degree of CMI
in the host response to infection.