Abstract

Leishmaniasis is a growing health problem in many parts of the world. Efforts to find new chemotherapeutics for leishmaniasis remain a priority. This study was carried out to determine the effect of using glucocorticoid drugs to reduce production of chemokine production in a bid to control Leishmania major infection in BALB/c mice. A total of 48 mice were used. In the therapeutic arm (post-infection), 24 mice were infected with L. major parasites. Six were treated with dexamethasone (0.69 mg/ml), another six hydrocortisone (2 mg/ml), six lipopolysaccharide (LPS) (10 ng/ml) and six phosphate-buffered saline (PBS) for 28 days and lesion development monitored for five weeks. For immunoprophylaxia (pre-infection), 24 other mice were treated with the same drugs and then infected with L. major. LPS was used as the positive control while PBS was the negative. Serum samples were collected for cytokine analysis for MIP 1α, MCP 1 and IFNγ using enzyme linked immunosorbent assay (ELISA). Parasite quantification was done by calculating the leishmania donovan unit (LDU). Lesion measurement was done by use of a vernier caliper. Lesion sizes after infection of BALB/c mice were similar in all the chemotherapeutic experimental groups till the onset of therapeutic treatments (P > 0.05). At 0.5 months post-treatment, significant differences (P < 0.05) were discerned in the lesion sizes of the BALB/c mice in the control groups. Generally, hydrocortisone gave better results as compared to dexamethasone. Both hydrocortisone and dexamethasone resulted in substantial clearance of parasitemia from both the lesions on footpads and spleens of infected BALB/c mice. They also led to significantly reduced levels of MCP 1 and MIP-1α and high levels of IFN γ. We show that glucocorticoids substantially reduce parasitemia in Leishmania infected mice by decreasing production of MCP 1 and MIP-1α chemokines while increasing IFN γ levels. In this regard, a further investigation into the modes of action of the glucocorticoids and probably their efficacy against other Leishmania strains should be explored further.

Key words: MIP-1α, MCP-1, dexamethasone, hydrocortisone, glucocorticoids (GCs), Leishmania.