The mechanism is dependent on TLR4 and functionally active granulocyte enzymes.8, 10 In rodents anti-CII induce CAIA after injection of lipopolysaccharide (LPS), a TLR4 ligand, and the ensuing polyarthritis is associated with PMN activation and can be ameliorated with a serine protease inhibitor, implying a central pathogenetic role for PMN.31, 32 The central role for TLR4 that we have described in anti-CII IC-induced production of chemokines is intriguing, as it represents an autoantibody-dependent mechanism that probably not is epitope dependent. Here, TLR4 is linked to polyarticular arthritis.