Modulation of the IL-6 System and STAT-3 Activation in Lymphocytes of Lean and Obese Women

Chronically elevated levels of interleukin-6 and active signal transducer and activator of transcription -3 are linked to inflammatory diseases, including cancer. Inflammation also becomes chronic in obesity as adipose tissue expands in response to nutrient excess. Obesity’s chronic inflammatory environment is characterized by changes in production of a host of mediators by immune cells and adipocytes. Among these are interleukin-6, the adipokines leptin and adiponectin, and signal transducer and activator of transcription -3, whose activators include interleukin-6 and leptin. Obesity is associated with increased levels of interleukin-6, but whether obesity modulates other components of the interleukin-6 system – namely, soluble interleukin-6 receptor and soluble glycoprotein 130 – and alters responsivity to interleukin-6 remains to be investigated. The purpose of this study was to examine if obesity is associated with alterations in constituents of the interleukin-6 system and to evaluate the association between obesity and the presence of active signal transducer and activator of transcription -3 in peripheral lymphocytes. Plasma from forty women across a body mass index spectrum was evaluated for interleukin-6 system constituents, adipokines, and C-reactive protein levels. Heparinized blood was stimulated with increasing amounts of interleukin-6 and the presence of active signal transducer and activator of transcription -3 in lymphocytes was evaluated. Results of our investigation show that plasma interleukin-6 levels significantly increased with increasing body mass index but plasma soluble interleukin-6 receptor and soluble glycoprotein 130 did not. Increasing interleukin-6 levels correlated with both leptin and C-reactive protein. Additionally, percentage of unstimulated lymphocytes positive for active signal transducer and activator of transcription -3 correlated with increasing body mass index, IL-6, and leptin. Finally, response to exogenous interleukin-6 stimulation was maintained by lymphocytes as body mass index increased, indicating that lymphocytes adapt to continue their role of immune defense in obesity. In sum, our results suggest that constitutively active signal transducer and activator of transcription -3 via interleukin-6 and leptin may increase risk of pathology, including cancer, in the obese.