Systemic inflammation activates the nuclear factor-kappaB regulatory pathway in adipose tissue.

Adipose tissue (AT) is a store of energy but also an endocrine organ with the capacity to produce and release proinflammatory mediators into the circulation. The mechanism that may trigger human AT inflammation on a cellular level still remains largely unknown. The aim of this study was to investigate whether an acute systemic inflammation increases AT inflammatory activity, focused on innate immunity. Open heart surgery results in an extensive acute systemic inflammation. Therefore, we investigated the in vivo gene expression and production of inflammatory mediators in omental and subcutaneous AT stimulated by surgery. Biopsies from omental and subcutaneous AT were collected before and after cardiopulmonary bypass. Blood samples were collected at the same time as the AT biopsies and plasma IL-6 levels were measured with ELISA. RT-PCR was used for quantification of relative AT gene expression. To verify the gene expression results on a protein level, we used immunohistochemistry and microdialysis. After surgery, in both omental and subcutaneous AT, there was a strong upregulation of nuclear factor-kappaB-regulated genes, e.g., chemokine ligand-2, E-selectin, IL-1beta, IL-6, IL-8, and Toll-like receptor-2. Immunohistochemistry showed staining for E-selectin associated with a high number of macrophages in close contact with and in the vascular wall. Increased levels of IL-6 were detected in microdialysate from subcutaneous AT. In conclusion, we present the novel finding that this model of inflammation induced a strong inflammatory response in both omental and subcutaneous AT including adhesion of macrophages to an activated endothelium and release of IL-6 from AT interstitium. It can be hypothesized that AT exerts a modulatory effect on innate immunity in humans.