BONE-MARROW NITRIC-OXIDE PRODUCTION AND DEVELOPMENT OF ANEMIA IN TRYPANOSOMA BRUCEI-INFECTED MICE

Mice infected with Trypanosoma brucei rapidly develop anemia, with the number of circulating erythrocytes reduced by 50% within a week after infection. The present study investigated the relationship between an emia and bone marrow nitric oxide (NO) production, Bone marrow cell po pulations from T. brucei-infected mice exhibited elevated levels of NO synthase activity which was inhibitable by N-G-nitro-L-arginine methy l ester. NO production was found to coincide,vith suppressed bone marr ow T-cell proliferation in response to stimulation with the mitogen co ncanavalin A both in vitro and in vivo, As this indicated that NO may inhibit proliferation in other cell types, particularly hemopoietic pr ecursors, we examined the role of NO in anemia during trypanosome infe ction. NO production correlated directly with the development of anemi a, and treatment of infected mice with N-G-nitro-L-arginine methyl est er in vivo to systemically inhibit NO synthesis led to a significant r eduction in the anemia, Thus, elevated NO production in the bone marro w of T. brucei-infected mice is likely to play a significant role in t he anemia resulting from T. brucei infection.