01994nas a2200241 4500000000100000008004100001260000900042653001200051653001800063653002600081653001800107653002600125653000900151653002400160653002900184653003100213100001200244245009400256300001200350490000700362520136900369022001401738 1991 d c199110aAnimals10aImmunotherapy10aInfusions, Parenteral10aInterleukin-110aMacrophage Activation10aMice10aMice, Inbred BALB C10aMycobacterium Infections10aMycobacterium lepraemurium1 aDenis M00aRecombinant interleukin-1 infusion increases resistance of BALB/c mice to murine leprosy. a897-9020 v133 a

BALB/c mice were infected by the subcutaneous route with 10(7) Mycobacterium lepraemurium (MLM), and the progression of the infection followed in mice injected i.p. with diluent or recombinant human recombinant interleukin-1 alpha (IL-1 alpha). It was observed that infusion of 1 microgram of IL-1 alpha per day led to a reduction of bacterial growth in the livers and popliteal lymph nodes of MLM injected mice (2-3-log reduction at 6 months, P less than 0.0001). There was no indication that IL-1 alpha infusion was acting by enhancing macrophage activation. Indeed, resident peritoneal macrophages from control infected mice were as competent as macrophages from infected mice treated with IL-1 alpha in generating superoxide anion (O2-) (approximately 400 nM O2-/h/mg at 2 months post-infection). Moreover, they were no more permissive than those of IL-1 alpha infused mice for MLM in vitro as both groups of cells allowed progressive MLM growth, i.e. a 20-fold enhancement of intramacrophage MLM growth. Infusion of IL-1 alpha during MLM infection was not associated with any abrogation of the suppression of the T-cell response to T-cell mitogens or specific stimulation with antigens which is complete at 1 month post-infection. It is concluded that IL-1 alpha has immunotherapeutic potential in leprosy with the mechanism(s) of action still unclear.

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