Indomethacin treatment slows disease progression and enhances a Th1 response in susceptible BALB/c mice infected with Leishmania major

Prostaglandins of the E series inhibit the development of Th1 responses. Wh en infected with Leishmania major, BALB/c mice fail to develop a Th1 respon se, but instead mount a Th2 response and die of the disease. Therefore, we treated L. major-infected BALB/c mice with indomethacin, which inhibits pro staglandin production. Indomethacin lessened disease severity (parasite bur den and pathology), and promoted a Th1 response, but the mice still succumb ed 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/e mice that was of the same magnit ude as the Th1 response observed in C57BL6 mice infected with L. major.