Classically (M1) and alternatively (M2) activated macrophages induce pro-fibrotic cytokines such as TGF-β and IL-6 and TIMPs production, fibroblast activation, and collagen production and collagen deposition, and macrophages play a pivotal role in the development of fibrosis in SSc [63,67]. This evidence concerns the gene IL6 and systemic sclerosis.