The link of biocompatibility to cytokine production

Recent studies suggest that chronic inflammation plays a role in the pathog enesis of cardiovascular disease. Cytokines released from jeopardized tissu es stimulate the liver to synthesize acute phase proteins, including C-reac tive protein (CRP). Baseline levels of CRP in apparently healthy persons or in persons with unstable angina constitute an independent risk factor for cardiovascular events. Mon recently, it has been suggested that CRP is usef ul not only as a marker of the acute phase response, but is also involved i n the pathogenesis of the disease. CRP may, in fact, directly interact with the atherosclerotic vessels or ischemic myocardium by activation of the co mplement system, thereby promoting inflammation and thrombosis. Several stu dies in uremic patients have implicated CRP as a marker of malnutrition, re sistance to erythropoietin, and chronic stimulation in hemodialysis. An inc reased cytokine production secondary to blood interaction with bioincompati ble dialysis components has been reported by several studies; interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and mainly IL-6 are the t hree proinflammatory cytokines involved in the pathogenesis of hemodialysis -related disease. We have provided evidence for the occurrence of high CRP and IL-6 levels in chronic dialytic patients exposed to contaminate dialysa te and suggest that backfiltration may induce a chronic, slowly developing inflammatory state that may he abrogated by avoiding backfiltration of cont aminate dialysate. Therefore, CRP is implicated as a marker linking bioinco mpatibility associated with backfiltration and increased cytokine productio n with a clinical state of chronic inflammation.