Abstract 4006: TNF-Alpha Production Following Toll-Like Receptor Stimulation and CD11b Expression on Monocytes is Related to Body-Mass Index in Atherosclerotic Patients
Background: Toll-like receptors (TLRs) are key players in innate immunity and are causally related to atherosclerosis, arterial remodeling and neointima formation. Ligand binding of TLRs results in the production of pro-inflammatory cytokines like TNF-α. The metabolic syndrome is an important combination of cardiovascular risk factors of which obesity is regarded a major hallmark. Previous research has shown an increased inflammatory state in patients suffering from the metabolic syndrome, however the role of TLRs in the metabolic syndrome is poorly understood. We studied the response following TLR stimulation in relation to body-mass index (BMI).
Methods: One hundred patients eligible for percutaneous coronary intervention were grouped according to BMI<25 or BMI>25. A blood sample was drawn immediately following sheath insertion. Whole blood samples were incubated overnight with TLR2 and TLR4 ligands Pam3Cys (50, 500 and 5000 ng/ml) and lipopolysaccharide (LPS, 1, 10 and 100 ng/ml). TNF-α levels were determined with an ELISA. In 52 patients CD11b expression on monocytes was measured using flow cytometry. CD11b is part of the MAC-1 receptor which is an important adhesion molecule for transendothelial migration and upregulated upon monocyte activation.
Results: The mean TNF-α production following Pam3Cys and LPS stimulation, and the mean CD11b expression were significantly higher in patients with BMI>25 in comparison to patients with BMI<25 (table 1⇓). A subsequent analysis of the CD11b expression showed that the increase in CD11b expression was most evident when BMI>30 (p=0.046).
Conclusion: Patients with an elevated BMI have a significantly increased TNF-α production following TLR-ligand stimulation and increased CD11b expression on circulating monocytes. These results point to a role for the innate immune system in the pathophysiology of the metabolic syndrome.