Plasma Chemokine and Chemokine-Autoantibody Complexes in Health and Disease

Free cytokine and chemokine concentrations in normal human serum are generally below the detection limit. For IL-8, this limit is about 6 pm. In one study, with an ELISA of higher sensitivity, mean serum IL-8 concentration was 2 ± 0.2 pm. Measurement of autoantibody and immune complex in normal human serum suggests a distinction between cytokines and chemokines. Free serum autoantibody to IL-1alpha, TNF-alpha, IFN-gamma, and IL-6 have been found, whereas serum cytokine immune complexes have generally not been described. In contrast, IL-8 and MCP-1 immune complexes have been detected in all normal sera (mean concentrations for 48 sera of 220 and 330 pm, respectively), whereas free autoantibody is not found in the majority of normal sera. Analysis of MCP-1 immune complexes indicates that the antibody is of high affinity, which is consistent with our inability to detect free antigen in the serum. It will be of interest to look for other chemokine serum immune complexes, to determine if the data for IL-8 and MCP-1 apply to chemoattractant cytokines generally. A central question is whether autoantibody plays a regulatory role as a sink for circulating cytokine or chemokine. This can perhaps be answered by testing for cytokine activity of immune complexes.