EFFICACY OF GLUCOCORTICOIDS IN CONTROLLING LEISHMANIA MAJOR INFECTING BALB/C MICE

Abstract

Leishmaniasis is a growing health problem in many parts of the world. Efforts to find new chemotherapeutics forleishmaniasis remain a priority. This study was carried out to determine the effect using glucocorticoid drugs toreduce production of chemokine production in a bid to control Leishmania major infection in BALB/c mice.A totalof 48 mice were used. In the therapeutic arm (post‐infection), 24 Mice were infected with L major parasitesweretreated with dexamethasone (0.69 mg/ml), hydrocortisone (2mg/ml) LPS (10 ng/ml) and PBS for 28 days and lesiondevelopment monitored for five weeks. For immunoprophylaxia (pre‐infection), 24 other mice were treated withthe above drugs and then infected with L major. LPS was used as the positive control while PBS was the negative.Serum samples were collected before and after infection for cytokine analysis for MIP 1α, MCP 1 and IFNγ usingELISA. Parasite quantification was done by calculating the LDU. Lesion measurement was done by use of a verniercaliper.Lesion sizes after infection of BALB/c mice were similar in all the experimental groups till the onset oftherapeutic treatments (P > 0.05). At 0.5 months post‐treatment, significant differences (P < 0.05) were discernedin the lesion sizes of the BALB/c mice in the control groups. However, hydrocortisone and dexamethasone causedsubstantial elimination of the parasites from the lesions and significantly reduced parasite burden in spleencompared to the controls at the end of the experiment. Generally, hydrocortisone gave better results as comparedto dexamethasone. Both hydrocortisone and dexamethasone resulted in substantial clearance of parasitemia fromboth the lesions on footpads and spleens of infected BALB/c mice. They also led to significantly reduced levels ofMCP 1 and MIP‐1α and high levels of IFN γ. These results show that glucocorticoids substantially reduceParasitemia in Leishmania infected mice by decreasing production of MCP 1 and MIP‐1α chemokines whileincreasing IFN γ levels. In this regard, a further investigation into the modes of action of the glucocorticoids andprobably their efficacy against other Leishmania strains should be explored further.