A nitric oxide synthase inhibitor reduces inflammation, down-regulates inflammatory cytokines and enhances interleukin-10 production in carrageenin-induced oedema in mice.
Mice injected in the footpad with carrageenin developed local inflammation which peaked at 48 hr. This delayed-type footpad swelling was significantly reduced in mice injected intraperitoneally (i.p.) with a specific nitric oxide (NO) synthase inhibitor, L-NGmonomethyl-arginine (L-NMMA). The draining lymph node (DLN) cells from mice injected 48 hr previously with carrageenin produced significantly higher levels of proliferation and interleukin-1 (IL-1), IL-2, IL-6 and interferon-gamma (IFN-gamma), but less IL-10, compared to cells from saline-injected controls, when stimulated with concanavalin A (Con A) in vitro. Treatment 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 secretion of IL-10. These data demonstrate that NO plays a significant role in local inflammation and the pattern of cytokines induced in this model.
Department of Immunology, University of Glasgow, U.K.
A
A
Ianaro
C A
CA
O'Donnell
M
M
Di Rosa
F Y
FY
Liew
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000627:therapeutic use; D002351:Carrageenan; D015536:Down-Regulation; D004342:Drug Hypersensitivity / Q000209:etiology / Q000517:prevention & control; D004487:Edema / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control; D007249:Inflammation / Q000517:prevention & control*; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019323:omega-N-Methylarginine
D007378:Interleukins; D016753:Interleukin-10; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D002351:Carrageenan; D001120:Arginine