Diphencyprone reduces the CD8+ lymphocytes and IL-4 and enhences IgG2a/IgG1 ratio in pathogenicity of acute leishmania major infection in BALB/c mice

Abstract

Background

The exact role of different immune cells and cytokines in control or promotion of intracellular growth of leishmania has still remained a controversial topic. The aim of the present study was to study effects of cellular changes and relevant cytokines in cell mediated immunity by diphencyprone (DCP) in pathogenicity of acute L.major infection in BALB/c mice.

Methods

45 healthy female BALB/c mice were injected with L. major promastigotes under the base of tail. The mice were randomly divided to three groups of 15 mice: (1) control group without any treatment. (2) acetone group: Acetone was applied topically on the cutaneous lesions weekly and (3) DCP group: DCP was applied topically on the cutaneous lesions with increasing concentrations to induce local allergy. The mice were followed by the end of eighth week, and then macroscopic changes, histopathology, immunology studies, and organ parasite burden were determined.

Results

In DCP group, in comparison to other groups the ulcer size and parasite burden in ulcer site and spleen increased, significantly. There was a deep lymphohistiocytic infiltration in the ulcer site. Total IgG, IgG1, and IgG2a levels as well as IgG2a/IgG1 ratio and intracellular IFN-gamma in CD8⁺ lymphocytes were significantly higher. IL4 and T CD8⁺ lymphocytes were significantly lower in DCP group. The IgG2a/IgG1 ratio was more than 1 in all groups.

Conclusion

Our findings demonstrated that DCP reduced the CD8⁺ lymphocytes and IL-4 production. In spite of increased IgG2a/IgG1 ratio, the parasite burden and inflammation severity increased in infected mice. The results can show the pivotal role of CD8⁺ lymphocytes in conjunction with Th1 lymphocytes in the control of acute leishmania infection in mice.