Effects of dexamethasone and hydrocortisone in the control of Leishmania major infection in BALB/c mice

Abstract

Leishmania is an obligate intracellular parasite that has to survive a hostile environment created by an infected host cell. There are many strains of Leishmania with different clinical presentations. Cutaneous leishmaniasis is the most common form of leishmaniasis and is manifested by skin lesions. The parasite has evolved many mechanisms to evade the immune system and propagate itself. One of the mechanisms is the induction of pro-inflammatory cytokines MIP 1α and MCP 1 which recruit more cells to area of infection leading to propagation of infection and pathology. This study was hereby aimed at determining the effects of dexamethasone and hydrocortisone in the control of L. major infection and their effect on the levels of MIP 1α and MCP 1 chemokines and the subsequent effect on the infection. The effects of glucocorticoids in the control of Leishmania major infection was investigated in both in vitro and in vivo experiments. Macrophages were treated with glucocorticoids (dexamethasone and hydrocortisone succinate).The macrophages were then infected with Leishmania major promastigotes and the levels of macrophage inflammatory protein 1α (MIP 1α), monocyte chemo-attractant protein-1 (MCP 1) chemokines were measured both before and after infection. Parasite multiplication in vitro was investigated by counting the number of amastigotes infecting treated and untreated macrophages (controls). For the in vivo experiment, Mice were treated with dexamethasone and hydrocortisone for 21 days then infected with Leishmania major parasites. Another group of mice was infected with Leishmania major promastigotes, monitored for lesion development for five weeks and then treated with glucocorticoids. Serum samples were collected from both arms of the experiment for cytokine analysis. Lesion development was also monitored for five weeks. Lesion sizes after infection of BALB/c mice were similar in all the experimental groups till the onset of treatment (P < 0.05). Two weeks after start of treatment, significant differences (P < 0.05) were discerned in the lesion sizes of the BALB/c mice in all the treatment groups. Both dexamethasone and hydrocortisone caused significant (P < 0.05) elimination of the parasites from the lesions and significantly reduced parasite burden in the spleen compared to the non- treated controls at the end of the experiment. Hydrocortisone and Dexamethasone significantly (P < 0.05) reduced the production of MIP 1Α 1α and MCP 1 1 chemokines both in experiments before infection and those after. They on the other hand significantly increased the production of IFNγ. Hydrocortisone gave the best results as compared to dexamethasone both in parasite elimination and in reduction of chemokine production with an exponential increase in IFN γ production. The results of this study demonstrate that Glucocorticoids control L. major infection in mice evidenced by reduction of parasite burden and elimination from lesions and also reduction of chemokine production limiting spread of infection. In this regard, i recommend the use of dexamethasone and hydrocortisone in the management of cutaneous leishmaniasis.