1) The IL-6/STAT3/Smad3 axis has profibrotic effects. 2) IL-6 inhibits apoptosis of IPF-derived fibroblasts and promotes apoptosis of normal fibroblasts. 3) High levels of IL-6 and IL-8 are early features of AE-IPFs and are associated with worse outcome. Here, SMAD3 is linked to idiopathic pulmonary fibrosis.