A team from the Leishmaniasis and Chagas Disease Unit , at the ISCIII National Center for Microbiology, has just published in the journal Plos Neglected Tropical Diseases an investigation carried out in a mouse model in which the effect of immunosuppressive drugs on the immune response in cases of visceral leishmaniasis. The results indicate that mice affected by this disease show different immune responses to different types of immunosuppressive treatments, and offer new knowledge to study how the effect of certain drugs can influence the severity of Leishmania infection in people.

Phlebotomus papatasi sand fly–a vector of leishmaniasis
Image/CDC

Visceral leishmaniasis is an infectious disease with a particularly high prevalence in immunosuppressed patients, caused by protozoa of the Leishmania family and characterized by chronic fevers, continued enlargement of the spleen (splenomegaly), and an abnormally high concentration of gamma globulin protein in the blood. If not diagnosed and treated early, it can be a fatal disease, leading to muscle atrophy, hepatomegaly, gastrointestinal bleeding, and secondary bacterial infections. Pentavalent antimonials, liposomal amphotericin B, and miltefosine are used for the treatment of visceral leishmaniasis.

In this study, researchers from the Leishmaniasis and Chagas Disease Unit of the National Center for Microbiology, a WHO collaborating center for leishmaniasis, are trying to better understand how drugs that suppress the action of the immune system, which many patients take for treats his autoimmune diseases, in the development of visceral leishmaniasis. For this they have used mice experimentally infected with this disease.

In order to learn how immunosuppressive drugs affect an immune system infected by Leishmania, the mice received treatment with methylprednisolone, anti-tumor necrosis factor (anti-TNF) antibodies and methotrexate, both before suffering from visceral leishmaniasis and a the disease has developed. The objective was to observe the reaction of the immune system, especially the reaction mediated by different cells necessary to eliminate the infection: interferons (IFN-y), cytokines (tumor necrosis factor TNF) and T-lymphocyte-producing interleukins (IL-2).

Different effects on the immune system

The researchers, led by Javier Moreno , observed that each drug had a different influence on these cells and, therefore, on the reaction of the immune system, and that the development of the parasite in different organs was also different depending on the type of immunosuppressive drug used.

Specifically, methotrexate and anti-TNF antibodies significantly reduced the presence of CD4 + T lymphocytes throughout the infection; furthermore, anti TNFs were also associated with a higher parasite load in the liver and a lower parasite load in the spleen. These consequences, together with a reduction in the number of cytokine-producing Th1 immune cells in the liver possibly associated with treatment, indicates the development of a more severe form of visceral leishmaniasis.

On the other hand, treatment with methylprednisolone and methotrexate caused a greater presence in the spleen of multiproducting T cells of cytokines specific for parasite antigens, and a lower parasite load compared to mice that did not receive any treatment (control group).

The authors, among whom are, in addition to Javier Moreno, Lorena Bernardo, Jose Carlos Solana, Alba Romero-Kauss, Carmen Sánchez and Eugenia Carrillo, conclude that these results show that the different immunosuppressive drugs have different effects on leishmaniasis infections visceral, and that the information obtained in this study could help improve treatment in patients, avoiding those immunosuppressants that may be associated with a greater severity of the infection.