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Prostaglandins of the E series inhibit the development of Th1 responses. When infected with Leishmania major, BALB/c mice fail to develop a Th1 response, but instead mount a Th2 response and die of the disease. Therefore, we treated L. major-infected BALB/c mice with indomethacin, which inhibits prostaglandin production. Indomethacin lessened disease severity (parasite burden and pathology), and promoted a Th1 response, but the mice still succumbed to infection. The explanation for these observations may be two-fold: (1) the beneficial effects of indomethacin were predominantly observed later in infection (beyond two weeks), a time at which indomethacin was unable to sufficiently block the development of a Th2 response; (2) indomethacin was unable to induce a Th1 response in BALB/c mice that was of the same magnitude as the Th1 response observed in C57BL/6 mice infected with L. major.

The degree of resistance to a local Leishmania amazonensis challenge has been compared in lines of mice obtained by selective breeding for high or low immunoresponsiveness: High and Low antibody responder mice of Selections I and II (HI, HII and LI, LII lines) and high and low responder mice to T mitogen PHA (Hi/PHA and Lo/PHA). The aim of this preliminary study was to focus attention on genetic differences related with well defined immune characteristics. Clear-cut results were obtained, both HI and HII mice developed large and disseminating lesions, the rate of symptom aggravation being faster in HII, while LI and LII proved resistant to parasites, only small and transient lesions being observed for them during a 150 days follow up. The outcome of infection also differs in Hi/PHA and Lo/PHA mice, Hi/PHA having a resistant and Lo/PHA a susceptible phenotype.