A NITRIC-OXIDE SYNTHASE INHIBITOR REDUCES INFLAMMATION, DOWN-REGULATES INFLAMMATORY CYTOKINES AND ENHANCES INTERLEUKIN-10 PRODUCTION IN CARRAGEENAN-INDUCED EDEMA IN MICE

Mice injected in the footpad with carrageenin developed local inflamma tion which peaked at 48 hr. This delayed-type footpad swelling was sig nificantly reduced in mice injected intraperitoneally (i.p.) with a sp ecific nitric oxide (NO) synthase inhibitor, L-N(G)monomethyl-arginine (L-NMMA). The draining lymph node (DLN) cells from mice injected 48 h r previously with carrageenin produced significantly higher levels of proliferation and interleukin-1 (IL-1), IL-2, IL-6 and interferon-gamm a (IFN-gamma), but less IL-10, compared to cells from saline-injected controls, when stimulated with concanavalin A (Con A) in vitro. Treatm ent of the carrageenin-injected mice with L-NMMA had little effect on the proliferative response of the DLN cells, but significantly reduced the production of IL-1, IL-2, IL-6 and IFN-gamma, and increased the s ecretion of IL-10. These data demonstrate that NO plays a significant role in local inflammation and the pattern of cytokines induced in thi s model.