C-reactive protein is an important immunoregulatory molecule that decreases systemic inflammatory response and ameliorates autoimmune disease

C-reactive protein (CRP) is an ancient member of the innate immune system. CRP is also a member of the pentraxin family of proteins and is a strong acute phase reactant in man. CRP has been shown to bind to phagocytes through interaction with Fcγ receptors, to affect the production of cytokines, and to enhance phagocytosis. CRP has been shown to protect mice from infection, to bind to nuclear antigens and to delay the onset of systemic lupus erythematosus (SLE) in autoimmune mice. The mechanism for these diverse effects has remained obscure. Both CRP and serum amyloid P (SAP) have been shown to bind to nuclear antigens that are targets of autoantibodies in patients with SLE. Additional studies have shown that CRP and SAP can mediate the uptake and clearance of apoptotic cells. These studies suggested that the pentraxins might prevent exposure and reactivity of the immune system to self-antigens. Our studies have shown that CRP and SAP can delay the onset of autoimmune disease accelerated by the injection of chromatin into autoimmune mice. More recently, it has been demonstrated that expression of human CRP as a transgene on autoimmune disease can delay the onset of autoimmune disease. We report now that a single injection of CRP can delay the onset of proteinuria in NZB × NZW female mice. In all three cases, CRP failed to substantially decrease anti-DNA autoantibodies yet protected mice from glomerular injury and death. We suggest that CRP delays the onset of autoimmune disease by modulating the effect of immune complexes on inflammatory cells. As we have shown recently, the anti-inflammatory effect of CRP in the lipopolysaccharide challenge model requires Fcγ receptor expression. It is proposed that CRP mediates protection from nephritis in SLE by the induction of anti-inflammatory cytokines and altering the reactivity of macrophages to inflammatory stimuli.