C-reactive protein in wealthy subjects: Associations with obesity, insulinresistance, and endothelial dysfunction - A potential role for cytokines originating from adipose tissue?

C-reactive protein, a hepatic acute phase protein largely regulated by circ ulating levels of interleukin-6, predicts coronary heart disease incidence in healthy subjects. We have shown that subcutaneous adipose tissue secrete s interleukin-6 in vivo. In this study we have sought associations of level s of C-reactive protein and interleukin-6 with measures of obesity and of c hronic infection as their putative determinants. We have also related level s of C-reactive protein and interleukin-ti to markers of the insulin resist ance syndrome and of endothelial dysfunction. We performed a cross-sectiona l study in 107 nondiabetic subjects: (1) Levels of C-reactive protein, and concentrations of the proinflammatory cytokines interleukin-6 and tumor nec rosis factor-alpha, were related to all measures of obesity, but titers of antibodies to Helicobacter pylori were only weakly and those of Chlamydia p neumoniae and cytomegalovirus were not significantly correlated with levels of these molecules. Levels of C-reactive protein were significantly relate d to those of interleukin-6 (r=0.37, P<0.0005) and tumor necrosis factor-al pha (r=0.46, P<0.0001). (2) Concentrations of C-reactive protein were relat ed to insulin resistance as calculated from the homoeostasis model assessme nt model, blood pressure, HDL, and triglyceride, and to markers of endothel ial dysfunction (plasma levels of von Willebrand factor, tissue plasminogen activator, and cellular fibronectin), A mean standard deviation score of l evels of acute phase markers correlated closely with a similar score of ins ulin resistance syndrome variables (r=0.59, P<0.00005), this relationship b eing weakened only marginally by removing measures of obesity from the insu lin resistance score(r=0.53, P<0.00005). These data suggest that adipose ti ssue is an important determinant of a low level, chronic inflammatory state as reflected by levels of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein, and that infection with H pylori, C pneumoniae, and cyt omegalovirus is not. Moreover, our data support the concept that such a low -level, chronic inflammatory state may induce insulin resistance and endoth elial dysfunction and thus link the latter phenomena with obesity and cardi ovascular disease.