Treatment of two patients with diffuse cutaneous leishmaniasis caused by Leishmania mexicana modifies the immunohistological profile but not the disease outcome

Two patients with diffuse cutaneous leishmaniasis caused by Leishmania mexi cana were treated with two leishmanicidal drugs (pentamidine and allopurino l) combined with recombinant interferon-gamma restoring Th-1 favouring cond itions in the patients. Parasites decreased dramatically in the lesions and macrophages diminished concomitantly, while IL-12-producing Langerhans cel ls and interferon-gamma- producing NK and CD8+ lymphocytes increased in a r eciprocal manner. The CD4+/CD8+ ratio in the peripheral blood normalized. D uring exogenous administration of interferon-gamma the parasites' capacity to inhibit the oxidative burst of the patients' monocytes was abolished. Ev en though Th-1-favouring conditions were restored, both patients relapsed t wo months after therapy was discontinued. We conclude that the tendency to develop a disease-promoting Th-2 response in DCL patients is unaffected by, and independent of, parasite numbers. Even though intensive treatment in D CL patients induced Th-1 disease restricting conditions, the disease-promot ing immunomodulation of few persistent Leishmania sufficed to revert the im mune response.