Increased Levels of Endotoxin Core Antibodies and Decreased Levels of sCD 14 Indicate Chronic Endotoxemia in Coronary Artery Disease (CURES-127)

Abstract

Introduction: Endotoxin is hypothesized to play an important role in chronic inflammation associated with coronary artery disease (CAD). The activity of the endotoxin is determined by the relative levels of endotoxin core antibodies (EndoCab), LPS binding protein (LBP) and soluble CD14 (sCD14). Towards this end, we estimated EndoCab, LBP and sCD14 levels in subjects with CAD and correlated them with clinical parameters, serum hormones and cytokine levels. Methods: The study subjects were recruited from Chennai Urban Rural Epidemiology Study (CURES). Age and gender matched subjects with (n=46) and without (n=45) CAD were selected from Phase III of the study. The levels of serum lipopolysaccharide (LPS), EndoCab and its translocation markers (sCD14 and LBP) along with insulin, glucagon, adiponectin and leptin and pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β were measured by immuno-assays. Results: Quartile analysis showed significantly higher percentage of CAD subjects in the highest quartile of EndoCab (>26.6 EMU/ml) (CAD-24% Vs Controls 0%) and LPS (>65.05 EU/ml) (CAD-21% vs. Controls 4%), while a reverse trend was seen for sCD14 (>2198398.7 ng/ml) (CAD-1% vs. Control-24%) (p<0.01). LBP levels were not statistically different between the groups. While EndoCab levels showed positive association with LPS, LBP, sCD14, hsCRP, HOMA-IR and glucagon, sCD14 showed a negative association with most of these markers. Significant increase in the levels of pro inflammatory cytokines TNFα, IL-6 and IL-1β, was also observed in the CAD group when compared to the control. Conclusions: Significantly elevated levels of EndoCab and decreased levels of sCD14 indicate chronic endotoxin exposure in CAD subjects.