Clinical and Immunological Outcome in Cutaneous Leishmaniasis Patients Treated with Pentoxifylline

Abstract

Abstract. Pentoxifylline is a tumor necrosis factor-α (TNF-α) inhibitor that also attenuates the immune response and decreases tissue inflammation. The association of pentoxifylline with antimony improves the cure rate of mucosal and cutaneous leishmaniasis. In this randomized and double blind pilot trial, cure rate was higher, although not significant, in patients who received antimony plus pentoxifylline than in those patients receiving antimony plus placebo. A significant decrease in TNF-α and interferon-γ (IFN-γ) levels during therapy was more pronounced in the antimony plus pentoxifylline group, whereas CCL-3 (Chemokine [C-C motif] ligand 3) decreased similarly in both groups. The increased levels of CXCL-9 (Chemokine [C-X-C motif] ligand 9) during therapy were lower in the antimony plus pentoxifylline group. Therapy with pentoxifylline modifies cytokines and chemokines production, which may be associated with therapeutic outcome.

Atypical Manifestations of Cutaneous Leishmaniasis in a Region Endemic for Leishmania braziliensis: Clinical, Immunological and Parasitological Aspects

“…However, failure of antimony has been on the rise in the country. Whereas in the early 80`s only 10% of individuals with CL failed antimony therapy in Brazil [25], this figure has increased and now ranges from 44 to 53% [26]. A second course of treatment with antimony usually cures close to 100% of initially refractory CL patients.…”

A Potential Role for Mononuclear Phagocytes in Cutaneous Ulcer Development in Human Immunodeficiency Virus–Leishmania braziliensis Coinfection

“…19,20 TNF can be detected in very early phases of L. braziliensis infection, and the levels increase as mononuclear cells infiltrate the lesion. 21 Interestingly, although in this study, we could not detect TNF in PBMC culture of the HIV/CL patient, staining for TNF was observed in the ulcer from this individual.…”

Leishmaniasis treatment update of possibilities for drug repurposing

“…Pentoxifylline (Figure 11), a xanthine derivative used to treat peripheral vascular disease, inhibits tumor necrosis factor-α (TNF-α), attenuates the immune response and decreases tissue inflammation (181). This drug has been investigated alone or combined with meglumine antimoniate, mainly in cases of refractory mucocutaneous leishmaniasis or cutaneous leishmaniasis (17,(182)(183)(184). The lesions of patients with mucocutaneous leishmaniasis caused by L. braziliensis receiving the combination treatment healed faster than those of the patients treated with the antimonial alone (185).…”