Protective effect of leflunomide on the natural course of Leishmania major-induced disease in genetically susceptible BALB/c mice

Int J Immunopharmacol. 1995 Jun;17(6):481-8. doi: 10.1016/0192-0561(95)00028-z.

Abstract

Leflunomide has been reported as an immunomodulating agent which acts on a variety of cells including T- and B-lymphocytes. CD4+ T-lymphocytes are essential for the type of disease that develops after infection with the protozoan parasite Leishmania major. A variety of immunological interventions has been shown to modulate disease development. Therefore, the effect of leflunomide on the development of parasite-induced lesions and the ensuing immune response was investigated in genetically susceptible BALB/c mice. Oral feeding for 7 to 10 days of leflunomide (30 mg/kg per day) beginning 2 days prior to or at the day of infection led to the development of a stable resistant phenotype, i.e. to long-lasting (> 13 months) regression of the lesions and clinical cure. Starting leflunomide treatment 3 days after infection was ineffective. The main bioactive metabolite, 1726 B, did not inhibit viability or growth of L. major promastigotes and amastigotes in vitro. Quantitative analysis of CD4+ and CD8+ cells in spleens and lymph nodes of parasite-infected animals treated with leflunomide for 5 days showed no significant effect. In vitro, 1726 B dose-dependently inhibited growth of stimulated T-cells, which could not be restored by saturating amounts of exogenous IL-2 and IL-4. No effect was observed on the killing function of activated macrophages. Taken together, the data indicate that leflunomide is a potent prophylactic agent to prevent an otherwise lethal infection of BALB/c mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparasitic Agents
  • Antiprotozoal Agents / pharmacology*
  • Female
  • Genetic Predisposition to Disease
  • Immunity, Innate / genetics
  • Isoxazoles / pharmacology*
  • Leflunomide
  • Leishmania major / drug effects*
  • Leishmania major / growth & development
  • Leishmaniasis, Cutaneous / etiology
  • Leishmaniasis, Cutaneous / genetics
  • Leishmaniasis, Cutaneous / prevention & control*
  • Mice
  • Mice, Inbred BALB C

Substances

  • Antiparasitic Agents
  • Antiprotozoal Agents
  • Isoxazoles
  • Leflunomide