Abstract
Mucosal leishmaniasis (ML) is characterized by high production of inflammatory cytokines. Administration of pentoxifylline (PTX), an inhibitor of TNF-alpha, with pentavalent antimony (Sb(v)), has been successfully used as alternative treatment for refractory ML. Our study aims to investigate the in situ cellular response underlying the effectiveness of this therapy, by evaluating the intensity of the inflammatory infiltrate, cellular composition, and expression of cytokines and granzyme A in lesions from ML before and after treatment with Sb(v) alone or in combination with PTX. Our data showed no differences in the intensity of inflammatory infiltrate comparing before and after treatment, and comparing between different treatments. However, although the number and frequency of CD4(+) and CD8(+) cells were not different before and after treatments or comparing different treatments, frequency of CD68(+) cells decreased after treatment with Sb(v) + PTX, but not with Sb(v). This was due to a reduction in CD68(+) TNF-alpha(+) and not in CD68(+) IL-10(+) cells. The frequency of TNF-alpha(+) cells was correlated with the intensity of the inflammatory infiltrate before treatment, but this correlation was lost after treatment with Sb(v) + PTX. Although the total expression of granzyme A did not significantly change after treatments, a clear trend of decrease was observed after treatment with Sb(v) + PTX. Interestingly, patients who took longer to heal, regardless of the treatment, displayed a higher frequency of granzyme A(+) cells. Our data suggest that treatment with Sb(v) + PTX acts in CD68(+) cells reducing the expression of TNF-alpha but not IL-10, resulting in more efficient modulation of the inflammatory response, accelerating the healing process.