Cytokine control of Leishmania infection in the BALB/c mouse: enhancement and inhibition of parasite growth by local administration of IL-2 or IL-4 is species and time dependent.

The therapeutic potential of locally injected interleukin-2 (IL-2) or interleukin-4 (IL-4) was studied in the footpads of Leishmania mexicana or Leishmania major infected BALB/c mice. The disease state was measured both pathologically, by measuring lesion size, and parasitologically, by counting total parasite numbers from infected footpads. IL-2 (0.5 microgram/dose) or IL-4 (0.1 microgram/dose) was administered either early, 1 day and/or 15 days after infection, or late, after palpable lesions had developed. Results differed markedly depending on which Leishmania species was used and at what time during the course of disease that therapy commenced. Both L. major and L. mexicana infections, as measured by footpad thickness and parasite number, were exacerbated if IL-4 was injected into the infected footpads early, during the first two weeks of infection. Paradoxically, late intralesional injection (i.e. after measurable lesions had developed) of IL-4 markedly inhibited both lesion size and parasite growth in L. major, though not L. mexicana, infected mice. IL-2 had no measurable effect on the course of L. major infections no matter when or how often, the infected footpads of mice were treated. However, early administration of IL-2 did exacerbate L. mexicana lesion and parasite growth while late treatment had no effect. Generally, but not always, increases in footpad size correlated with increases in parasite number.