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. 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.
D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D007111:Immunity, Cellular; D007213:Indomethacin / Q000627:therapeutic use*; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011448:Prostaglandin Antagonists / Q000627:therapeutic use; D018417:Th1 Cells / Q000276:immunology*