Successful Chemotherapy in Experimental Leishmaniasis Is Influenced by the Polarity of the T Cell Response Before Treatment

Abstract

Little is known about the influence of host factors on successful chemotherapy in leishmaniasis. Although successfully treated patients will convert from a delayed-type hypersensitivity (DTH)-negative to a DTH-positive state, the importance of the immune status of the host before treatment remains largely unexplored. In experimental murine cutaneous leishmaniasis, it was found that increased polarization towards a Th2 cytokine profile before the onset of drug therapy leads to an increased frequency of relapse after treatment. Whereas >50% of mice with established Leishmania major infections were cured when treated with the antileishmanial drug sodium stibogluconate, <10% of mice were cured when the animals had been pretreated with anti-interferon-γ antibody to polarize the response toward a Th2 cytokine pattern before therapy. With successful drug therapy, cytokine profiles were found to switch from a Th2 to Th1 pattern, and resistance to reinfection was observed.