Abstract

Introduction: Adult patients with Paracoccidioidomycosis (PCM) exhibit pulmonary involvement characterized by chronic inflammation and residual fibrosis. The simultaneous use of pentoxyfilline (PTX) and antifungal therapy in an experimental PCM model resulted in a statistically significant reduction of both inflammation and fibrosis, but the effect of PTX monotherapy on the host response to Paracoccidioides brasiliensis (Pb) has not been well documented. Our aim was to determine PTX effects on both the course of pulmonary lesions and the local immune responses in our experimental PCM model.਀㰀戀㸀䴀攀琀栀漀搀漀氀漀最礀㨀㰀⼀戀㸀 䴀愀氀攀 䈀䄀䰀䈀⼀挀 洀椀挀攀 眀攀爀攀 搀椀猀琀爀椀戀甀琀攀搀 椀渀琀漀 㐀 最爀漀甀瀀猀㨀 椀⤀ 椀渀琀爀愀渀愀猀愀氀氀礀 ⠀椀⸀渀⤀ 椀渀漀挀甀氀愀琀攀搀 眀椀琀栀 倀䈀匀 ⠀渀㴀㔀　⤀Ⰰ 椀椀⤀ 椀⸀渀 椀渀昀攀挀琀攀搀 眀椀琀栀 ㌀砀㄀　☀⌀㠀㜀㐀㌀㬀㘀 倀戀ⴀ挀漀渀椀搀椀愀 ⠀渀㴀㔀　⤀㬀 椀椀椀⤀ 椀⸀渀 椀渀漀挀甀氀愀琀攀搀 眀椀琀栀 倀䈀匀 愀渀搀 倀吀堀ⴀ琀爀攀愀琀攀搀 ⠀渀㴀㌀　⤀㬀 愀渀搀 椀瘀⤀ 倀戀ⴀ椀渀昀攀挀琀攀搀 倀吀堀ⴀ琀爀攀愀琀攀搀 洀椀挀攀 ⠀渀㴀㌀　⤀⸀ 倀吀堀ⴀ琀爀攀愀琀洀攀渀琀 猀琀愀爀琀攀搀 㐀ⴀ眀欀猀 瀀漀猀琀ⴀ椀渀昀攀挀琀椀漀渀 眀栀攀渀 最爀愀渀甀氀漀洀愀琀漀甀猀 椀渀昀氀愀洀洀愀琀椀漀渀 眀愀猀 愀氀爀攀愀搀礀 瀀爀攀猀攀渀琀㬀 倀吀堀 眀愀猀 愀搀洀椀渀椀猀琀攀爀攀搀 搀愀椀氀礀 昀漀爀 攀椀最栀琀 眀欀猀⸀ 吀攀渀 洀椀挀攀 瀀攀爀 最爀漀甀瀀 眀攀爀攀 愀渀愀氀礀稀攀搀 愀琀 琀栀攀 洀椀搀搀氀攀 愀渀搀 攀渀搀 漀昀 琀栀攀爀愀瀀礀 愀渀搀 昀漀甀爀 眀攀攀欀猀 瀀漀猀琀ⴀ琀爀攀愀琀洀攀渀琀 戀礀 栀椀最栀 爀攀猀漀氀甀琀椀漀渀 挀漀洀瀀甀琀攀搀 琀漀洀漀最爀愀瀀栀礀 ⠀䠀刀䌀吀⤀Ⰰ 栀椀猀琀漀瀀愀琀栀漀氀漀最礀⼀栀椀猀琀漀洀漀爀瀀栀漀洀攀琀爀礀 愀渀搀 愀 ㈀㄀ⴀ挀礀琀漀欀椀渀攀 戀椀漀瀀氀攀砀 愀猀猀愀礀⸀  Results: At the middle and end of treatment, Pb-infected-PTX treated mice showed a significant reduction of lung density when compared to Pb-infected-non treated mice, as assessed by quantification of Hounsfield Units on HRCT (p<0.05). Additionally, at the end of therapy, the lung area exhibiting inflammatory reaction by histomorphometry was only 3% vs. 22% in the non-treated group, respectively (p<0.05). and this reduction was associated with a lower fungal burden and limited collagen increment in the pulmonary lesions. PTX treatment restored the levels of IFN-γ,MIP-1β and IL-3 that had been down-regulated by Pb-infection. In addition, IL-12p70,IL-10,IL-13 and eotaxin were significantly increased whereas RANTES levels were decreased in the lung of Pb-infected-PTX treated mice when compared to the non-treated group. ਀㰀戀㸀䌀漀渀挀氀甀猀椀漀渀㨀㰀⼀戀㸀 吀栀椀猀 猀琀甀搀礀 猀栀漀眀攀搀 琀栀愀琀 倀吀堀 琀栀攀爀愀瀀礀 愀搀洀椀渀椀猀琀爀愀琀攀搀 愀琀 愀渀 攀愀爀氀礀 猀琀愀最攀 漀昀 最爀愀渀甀氀漀洀愀琀漀甀猀 椀渀昀氀愀洀洀愀琀椀漀渀 挀漀渀琀爀漀氀氀攀搀 倀䌀䴀 瀀爀漀最爀攀猀猀 戀礀 爀攀搀甀挀椀渀最 瀀甀氀洀漀渀愀爀礀 椀渀昀氀愀洀洀愀琀椀漀渀Ⰰ 昀甀渀最愀氀 戀甀爀搀攀渀 愀渀搀 愀氀猀漀Ⰰ 戀礀 愀瘀漀椀搀椀渀最 琀栀攀 愀瀀瀀攀愀爀愀渀挀攀 漀昀 挀漀氀氀愀最攀渀 搀攀瀀漀猀椀琀猀 椀渀 瀀甀氀洀漀渀愀爀礀 氀攀猀椀漀渀猀⸀ Financial support: COLCIENCIAS grants No 2213-408-20412 and 2213-04-16439. ਀䄀甀琀栀漀爀猀 ㄀ 愀渀搀 ㈀ 挀漀渀琀爀椀戀甀琀攀搀 攀焀甀愀氀氀礀 琀漀 琀栀椀猀 眀漀爀欀⸀㰀⼀昀漀渀琀㸀㰀⼀瀀㸀㰀戀爀㸀㰀戀㸀䬀攀礀眀漀爀搀㨀 㰀⼀戀㸀☀渀戀猀瀀㬀䤀洀洀甀渀漀洀漀搀甀氀愀琀椀漀渀Ⰰ 倀攀渀琀漀砀椀昀礀氀氀椀渀攀Ⰰ 倀甀氀洀漀渀愀爀礀 瀀愀爀愀挀漀挀挀椀搀椀漀椀搀漀洀礀挀漀猀椀猀㰀⼀琀搀㸀㰀⼀琀爀㸀㰀⼀琀愀戀氀攀㸀㰀⼀琀爀㸀㰀⼀琀搀㸀㰀⼀琀愀戀氀攀㸀㰀⼀戀漀搀礀㸀㰀⼀栀琀洀氀㸀