To further substantiate our finding that the mechanism of pirfenidone action is through increased IL-10 release from macrophages, which paves the way for alleviation of local and systemic injury in pancreatitis, we demonstrate that the salutary effects of pirfenidone are abrogated either in the absence of IL-10 (IL-10–KO mice) or reparative M2 macrophages (by depleting macrophages using clodronate liposomes in later phases of pancreatitis). This evidence concerns the gene IL10 and pancreatitis.