Pirfenidone inhibits cryoablation induced local macrophage infiltration along with its associated TGFb1 expression and serum cytokine level in a mouse model Journal Article

   

Authors:	Gu, Y.; Srimathveeravalli, G.; Cai, L.; Ueshima, E.; Maybody, M.; Yarmohammadi, H.; Zhu, Y. S.; Durack, J. C.; Solomon, S. B.; Coleman, J. A.; Erinjeri, J. P.
Article Title:	Pirfenidone inhibits cryoablation induced local macrophage infiltration along with its associated TGFb1 expression and serum cytokine level in a mouse model
Abstract:	Purpose: To investigate the effects of pirfenidone (PFD) on post-cryoablation inflammation in a mouse model. Materials and methods: In this IACUC-approved study, eighty Balb/c mice were randomly divided into four groups (20/group): sham + vehicle, sham + PFD, cryoablation + vehicle, and cryoablation + PFD. For cryoablation groups, a 20% freeze rate cryoablation (20 s to less than −100 °C) was used to ablate normal muscle in the right flank. For sham groups, the cryoprobe was advanced into the flank and maintained for 20 s without ablation. PFD or vehicle solution was intraperitoneally injected (5 mg/kg) at days 0, 1, 2, 3, and then every other day until day 13 after cryoablation. Mice were euthanized at days 1, 3, 7, and 14. Blood samples were used for serum IL-6, IL-10, and TGFβ1 analysis using electrochemiluminescence and ELISA assays, respectively. Immunohistochemistry-stained ablated tissues were used to analyze macrophage infiltration and local TGFβ1 expression in the border region surrounding the cryoablation-induced coagulation zone. Results: Cryoablation induced macrophage infiltration and increased TGFβ1 expression in the border of the necrotic zone, and high levels of serum IL-6, peaking at days 7 (70.5 ± 8.46/HPF), 14 (228 ± 18.36/HPF), and 7 (298.67 ± 92.63), respectively. Animals receiving PFD showed reduced macrophage infiltration (35.5 ± 16.93/HPF at day 7, p < 0.01) and cytokine levels (60.2 ± 7.6/HPF at day 14, p < 0.01). PFD also significantly reduced serum IL-6 levels (p < 0.001 vs. all non-PFD groups). Conclusions: PFD mitigates cryoablation induced muscle tissue macrophage infiltration, increased IL-6 levels, and local TGFβ1 expression in a small animal model. © 2018 Elsevier Inc.
Keywords:	macrophage; cryoablation; pirfenidone; il-6; tgfβ1
Journal Title:	Cryobiology
Volume:	82
ISSN:	0011-2240
Publisher:	Elsevier Inc.
Date Published:	2018-06-01
Start Page:	106
End Page:	111
Language:	English
DOI:	10.1016/j.cryobiol.2018.03.012
PROVIDER:	scopus
PUBMED:	29621494
PMCID:	PMC7464590
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85045211852&doi=10.1016%2fj.cryobiol.2018.03.012&partnerID=40&md5=06684693283cc72578a2074d4be25c44
Notes:	Article -- Export Date: 1 June 2018 -- Source: Scopus

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