RECOMBINANT INTERLEUKIN-1 INFUSION INCREASES RESISTANCE OF BALB/C MICE TO MURINE LEPROSY

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-mu-g 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 < 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-) (almost-equal-to 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.