Pentoxifylline down modulate in vitro Tcell responses and attenuate pathology in Leishmania and HTLV-I infections

Abstract

Tumor necrosis factor-α (TNF-α) is known to have numerous biological properties relating to inflammation. This cytokine participates in the tissue damage of chronic inflammatory, autoimmune and infectious diseases. Pentoxifylline is a methylxanthine that inhibits phosphodiesterase IV, which inhibits the degradation of the cAMP and prostanoids. The increased intracellular concentration of the cAMP leads to a negative regulation of NF-κB and NF-AT transcription factors and suppresses TNF-α production. This review describes studies that support evidences that TNF-α is involved in the pathogenesis of HTLV-1 associated myelopathy and of cutaneous and mucosal leishmaniasis. Additionally, it demonstrates the effect of pentoxifylline in vitro in inhibiting TNF-α and IFN-γ spontaneous production in PBMC from HTLV-1-infected patients, as well as its in vivo effect in inhibiting TNF-α in sera from mucosal leishmaniasis patients. Moreover, we review the results of clinical studies from the last 10 years using pentoxifylline to treat HTLV-1 associated myelopathy and cutaneous and mucosal leishmaniasis. © 2008 Elsevier B.V. All rights reserved.