MODULATION OF MURINE MACROPHAGE FUNCTION BY IL-13

Activated macrophages are important effector cells for immune response s to many parasites and immune responses are strongly modulated in par t by the effect of Th cell-derived cytokines on macrophages. Th1-deriv ed cytokines such as IFN-gamma are strong stimulators of macrophage ac tivation, while cytokines produced by Th2 cells, including IL-4 and IL -10, have been shown under some conditions to inhibit macrophage activ ities associated with inflammatory responses. IL-13, a recently descri bed cytokine produced by Th2 cells, is also capable of down-modulating macrophage activity in a manner similar to that previously described for IL-4. Treatment of activated macrophages with IL-13 reduces the pr oduction of inflammatory monokines in response to IFN-gamma or LPS, bo th potent stimulators of these factors. In addition, IL-13 decreases t he production of nitric oxide by activated macrophages. Nitric oxide h as been implicated in both macrophage cytotoxicity and macrophage-asso ciated immunosuppression. The suppression of nitric oxide by IL-13 lea ds to a decrease in parasiticidal activity by activated macrophages. H owever, our data indicate that IL-13 has plieotropic effects, while th e inflammatory potential of activated macrophages is significantly red uced, the potential of other macrophage subsets is unimpaired. These d ata indicate that IL-13 could be a potent modulator of immune response s in vivo, with effects that may embrace both macrophage suppressive a nd macrophage potentiating functions.