XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:170-1

Oral / Poster

170-1

EFFECTS OF FIBROSIS TREATMENT ON IMMUNOLOGICAL AND MYCOLOGICAL PARAMETERS IN EXPERIMENTAL PARACOCCIDIOIDES BRASILIENSIS INFECTION

Authors:

Eva Burger (USP - Universidade de Sao Paulo) ; Angela Satie Nishikaku (USP - Universidade de Sao PauloUNIFESP - Universidade Federal de Sao Paulo) ; José Vicente Alves (USP - Universidade de Sao Paulo) ; Liana Verinaud (UNICAMP - Universidade estadual de Campinas) ; Zoilo Pires Camargo (USP - Universidade de Sao Paulo) ; Jacy Gameiro (UNICAMP - Universidade estadual de Campinas) ; Cf Andrade (UNICAMP - Universidade estadual de Campinas) ; Dagmar Stach-machado (UNICAMP - Universidade estadual de Campinas) ; Raphael Molina (USP - Universidade de Sao Paulo)

Abstract

Fibrosis in patients infected with Paracoccidioides brasiliensis (Pb) leads to poor quality of life. We used a murine model to evaluate the effect of drugs that influence fibrosis: the cytokine γ-IFN; the antibiotic Tetracycline and the anti-inflammatory drug Lumiracoxib comparing with controls only infected with Pb. We collected organs of the mice and evaluated in situ the overall architecture of the granulomas, the local presence of collagen and its degradation product hydroxiprolin (HPro), levels of NO and of relevant cytokines to granuloma formation and maintenance and also quantified Pb with preserved or altered morphology.਀䄀琀㄀㔀搀愀礀猀愀昀琀攀爀椀渀昀攀挀琀椀漀渀Ⰰ 最ⴀ 䤀䘀一琀爀攀愀琀洀攀渀琀挀愀甀猀攀搀搀攀挀爀攀愀猀攀椀渀琀栀攀渀甀洀戀攀爀漀昀瘀椀愀戀氀攀倀戀椀渀瀀愀爀愀氀氀攀氀眀椀琀栀椀渀挀爀攀愀猀攀搀椀渀昀氀愀洀洀愀琀漀爀礀挀攀氀氀猀椀渀昀氀甀砀愀渀搀一伀Ⰰ 䤀䰀ⴀ㄀㈀Ⰰ ☀⌀㘀㄀㔀㐀㌀㬀ⴀ 䤀䘀一愀渀搀吀䜀䘀ⴀ☀⌀㘀㄀㔀㌀㠀㬀瀀爀漀搀甀挀琀椀漀渀Ⰰ 愀渀搀琀栀攀搀攀瀀漀猀椀琀椀漀渀漀昀琀栀椀挀欀挀漀氀氀愀最攀渀昀椀戀攀爀猀椀渀愀渀漀爀最愀渀椀稀攀搀Ⰰ 挀漀渀挀攀渀琀爀椀挀瀀愀琀琀攀爀渀Ⰰ 搀攀氀椀洀椀琀愀琀椀渀最琀栀攀氀攀猀椀漀渀⸀ 吀攀琀爀愀挀礀挀氀椀渀攀愀搀洀椀渀椀猀琀爀愀琀椀漀渀攀氀椀挀椀琀攀搀爀攀搀甀挀琀椀漀渀漀昀瘀椀愀戀氀攀昀甀渀最愀氀氀漀愀搀愀渀搀椀渀挀爀攀愀猀攀椀渀一伀Ⰰ 䜀䴀ⴀ䌀匀䘀愀渀搀䤀䰀ⴀ㄀㈀氀攀瘀攀氀猀⸀ 䄀渀琀椀ⴀ椀渀昀氀愀洀洀愀琀漀爀礀琀爀攀愀琀洀攀渀琀椀渀挀爀攀愀猀攀搀挀漀氀氀愀最攀渀猀礀渀琀栀攀猀椀猀Ⰰ 搀攀瀀漀猀椀琀攀搀椀渀愀搀椀猀愀爀爀愀礀攀搀瀀愀琀琀攀爀渀愀渀搀搀攀挀爀攀愀猀攀搀瀀爀漀搀甀挀琀椀漀渀漀昀一伀Ⰰ 眀栀椀挀栀爀攀猀甀氀琀攀搀椀渀昀甀渀最愀氀搀椀猀猀攀洀椀渀愀琀椀漀渀椀渀猀瀀椀琀攀漀昀椀渀挀爀攀愀猀攀搀吀一䘀ⴀ愀瀀爀漀搀甀挀琀椀漀渀⸀ At 120 days, -IFN significantly reduced viable fungal load but increased cellular influx, NO and IL-12 levels, eliciting the formation of compact granulomas. Tetracyclin increased the synthesis of HPro, NO and IL-12 as well as cellular influx and caused intense collagen deposition in a well organized pattern of concentric fibers, forming compact granulomas and providing confinement of the reduced numbers of Pb present. Lumiracoxib treatment resulted in infection exacerbation, with histological suggestion of unhindered dissemination of numerous Pb, due to the disorganized deposition of abundant collagen fibers in the granulomas, few inflammatory cells, low levels of NO and in spite of high concentration of -IFN. At this infection time, all treatments reduced TGF- production.਀伀甀爀爀攀猀甀氀琀猀猀甀最最攀猀琀琀栀愀琀琀栀攀戀攀猀琀椀渀搀椀挀愀琀漀爀猀漀昀挀漀渀琀爀漀氀漀昀瀀愀爀愀挀漀挀挀椀搀椀漀椀搀漀洀礀挀漀猀椀猀愀猀攀砀瀀爀攀猀猀攀搀戀礀猀甀挀挀攀猀猀昀甀氀氀漀挀愀氀倀戀氀礀猀椀猀愀爀攀琀栀攀瀀爀攀猀攀渀挀攀漀昀挀漀洀瀀愀挀琀最爀愀渀甀氀漀洀愀猀Ⰰ 搀攀氀椀洀椀琀攀搀戀礀愀挀漀渀琀椀渀甀漀甀猀搀攀瀀漀猀椀琀漀昀挀漀氀氀愀最攀渀琀礀瀀攀㄀愀爀爀愀渀最攀搀椀渀挀漀渀挀攀渀琀爀椀挀漀爀椀攀渀琀愀琀椀漀渀琀漀挀漀渀琀愀椀渀琀栀攀昀甀渀最椀Ⰰ 愀渀搀琀栀攀瀀爀漀搀甀挀琀椀漀渀漀昀栀椀最栀挀漀渀挀攀渀琀爀愀琀椀漀渀漀昀挀礀琀漀欀椀渀攀猀䤀䰀ⴀ㄀㈀愀渀搀最ⴀ䤀䘀一愀猀眀攀氀氀愀猀漀昀一伀⸀ 䈀愀猀攀搀漀渀琀栀攀猀攀瀀愀爀愀洀攀琀攀爀猀Ⰰ 眀攀挀愀渀挀漀渀挀氀甀搀攀琀栀愀琀琀栀攀爀愀瀀礀眀椀琀栀攀椀琀栀攀爀最ⴀ䤀䘀一漀爀吀攀琀爀愀挀礀挀氀椀渀攀猀攀攀洀猀瀀爀漀洀椀猀椀渀最Ⰰ 爀攀搀甀挀椀渀最琀栀攀昀甀渀最愀氀氀漀愀搀Ⰰ 椀渀挀爀攀愀猀椀渀最琀栀攀瀀爀漀搀甀挀琀椀漀渀漀昀一伀愀渀搀漀昀琀栀攀猀琀椀洀甀氀愀琀漀爀礀挀礀琀漀欀椀渀攀猀 ☀⌀㤀㐀㜀㬀ⴀ䤀䘀一愀渀搀䤀䰀ⴀ㄀㈀Ⰰ 搀攀挀爀攀愀猀椀渀最琀栀愀琀漀昀琀栀攀椀渀栀椀戀椀琀漀爀礀挀礀琀漀欀椀渀攀吀䜀䈀ⴀ☀⌀㤀㐀㘀㬀愀渀搀愀氀琀攀爀椀渀最琀栀攀最爀愀渀甀氀漀洀愀猀愀爀挀栀椀琀攀挀琀甀爀攀琀漀眀愀爀搀猀愀挀漀洀瀀愀挀琀猀琀爀甀挀琀甀爀攀琀栀愀琀瀀爀漀瘀椀搀攀猀倀戀挀漀渀琀愀椀渀洀攀渀琀眀椀琀栀漀甀琀攀砀挀攀猀猀椀瘀攀昀椀戀爀漀猀椀猀⸀ ਀䜀爀愀渀琀猀㨀䘀䄀倀䔀匀倀　㘀ⴀ㘀　　㤀㄀ⴀ㘀Ⰰ 　㜀⼀㔀㘀㜀㐀㔀ⴀ㌀愀渀搀䌀一倀焀㌀　㐀㘀㌀　⼀㈀　　㤀ⴀ㠀

Keyword: Fibrosis, Treatment, Tetracyclin, Gamma-IFN, Lumiracoxib

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