Modulation of murine macrophage function by IL-13.
Activated macrophages are important effector cells for immune response to many parasites and immune responses are strongly modulated in part by the effect of Th cell-derived cytokines on macrophages. Th1-derived cytokines such as IFN-gamma are strong stimulators of macrophage activation, while cytokines produced by Th2 cells, including IL-4 and IL-10, have been shown under some conditions to inhibit macrophage activities associated with inflammatory responses. IL-13, a recently described 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 production of inflammatory monokines in response to IFN-gamma or LPS, both potent stimulators of these factors. In addition, IL-13 decreases the production of nitric oxide by activated macrophages. Nitric oxide has been implicated in both macrophage cytotoxicity and macrophage-associated immunosuppression. The suppression of nitric oxide by IL-13 leads to a decrease in parasiticidal activity by activated macrophages. However, our data indicate that IL-13 has pleiotropic effects, while the inflammatory potential of activated macrophages is significantly reduced, the potential of other macrophage subsets is unimpaired. These data indicate that IL-13 could be a potent modulator of immune responses in vivo, with effects that may embrace both macrophage suppressive and macrophage potentiating functions.
Doherty
T M
TM
Department of Immunology, DNAX Research Institute for Cellular and Molecular Biology, Palo Alto, CA 94304.
Kastelein
R
R
Menon
S
S
Andrade
S
S
Coffman
R L
RL
D000818:Animals; D017951:Antigen Presentation; D000954:Antigens, Surface / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D005260:Female; D066298:In Vitro Techniques; D018793:Interleukin-13; D007378:Interleukins / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010587:Phagocytosis
D000954:Antigens, Surface; D016207:Cytokines; D018793:Interleukin-13; D007378:Interleukins