Wound Healing Society

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Pirfenidone Regulates Lps Mediated Hyper Activation Of Neutrophils
SHANKAR J EVANI, KAI P. LEUNG.
USAISR, Fort Sam Houston, TX, USA.

Excessive inflammation or abrogating inflammation may result in improper tissue recovery during infection/injury. Neutrophils are among the first respondents of innate immune system to arrive at the injury site and have been implicated in exacerbated inflammation during their fight against invading pathogens or tissue debridement for wound repair. Drugs with potential anti-inflammatory and anti-fibrotic effects are of promise in tissue recovery. Of interest, pirfenidone (Pf) an FDA approved anti-inflammatory/anti-fibrotic drug used in treating idiopathic pulmonary fibrosis was shown to ameliorate inflammation in some animal models. We have shown that Pf lessens the profibrotic phenotype of TGF-β1-stimulated human dermal myofibroblasts in vitro and also reduces pro-inflammatory cytokines in mouse burn wounds. However, there is a lack of understanding of Pf effect on neutrophils Here, we examined the effect of Pf (0.1, 0.5 & 1 mg/ml) on neutrophils treated with LPS (20ng/ml) as a model of non-sterile inflammation. Neutrophils from healthy donors were used (n = 6; Stats: One/two-way ANOVA) and we showed that 0.5mg/ml Pf at 4/16h post LPS treatment, lowered oxidative burst (MPO, ROS), degranulation (MMP8, MMP9, CD35, CD45) and inflammation (TNFα, IL-1β, IL-8, MCP-1, MIP-1α) without abrogating phagocytosis and NETosis. Pf decreased neutrophil chemotaxis to chemoattractant. We also showed that Pf acted on LPS - TLR axis by down regulating Kinases. In conclusion, the results support the notion that Pf could modulate neutrophil functions in vitro.Funding source: Congressionally Directed Medical Research Programs, U.S. Army Medical Research and Materiel Command W81XWH-15-2-0083 and the Naval Medical Research Center's Advanced Medical Development program (MIPRN3239815MHX040).


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