To investigate the effects of pirfenidone (PFD) on post-cryoablation inflammation
in a mouse model. 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 seconds 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 seconds 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. 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). PFD mitigates cryoablation induced muscle tissue
macrophage infiltration, increased IL-6 levels, and local TGFβ1 expression in a small
animal model.