Elevated TGF-beta levels in drug-resistant visceral leishmaniasis

BACKGROUND: Poor and neglected populations in Africa are particularly affected with visceral leishmaniasis. The widespread emergence of resistance to pentavalent antimonials occurs globally and the unavailability of a vaccine in clinical use constitutes a major obstacle in disease control. OBJECTIVE: To investigate the cytokine profile in human visceral leishmaniasis. DESIGN: A cross-sectional laboratory-based study. SETTING: Single center study carried out at the Institute of Endemic Diseases, University of Khartoum, Sudan. PATIENTS AND METHODS: Soluble lysates of L major and L donovani were used to stimulate the lymphocytes of two groups of confirmed VL patients (group 1 [n=20] had respond to pentostam treatment and group 2 [n=5] were recorded as drug resistant after follow up) in a cellular proliferation assay and the levels of IFNγ, IL-10, TNFα and TGFβ were detected by cytokine ELISA. MAIN OUTCOME MEASURES: Levels of IFNγ, TNFα, IL-10 and TGFβ. RESULTS: A significant increase of IFNγ and TNFα levels were reported in stimulated cells of drug susceptible and drug resistant groups, but no significant difference in IL-10 production was observed between the different antigens or between the patients groups. TGFβ from stimulated lymphocytes was secreted in statistically significant amounts in patients reported as drug resistant in response to both L major and L donovani antigens (P<.001). CONCLUSIONS: In VL patients, IFNγ and TNFα are extremely produced in response to in vitro re-stimulation which means that the parasitic infection, although virulent and chronic, does not render patients as immunocompromised. However, TGFβ is mostly associated with treatment failure. LIMITATIONS: This study assessed secretory TGFβ. A study with a larger sample size to assess TGFβ gene expression and to follow its intracytoplasmic synthesis in drug resistant VL patients is recommended.