Abstract
Background and AimAssessment of serum concentration of lipopolysaccharide (LPS)-binding protein (LBP) has been suggested as a useful biomarker to indicate activation of innate immune responses to microbial products. We investigated LBP concentrations and associations with demographics, lifestyle factors, and common metabolic abnormalities in adults. We also examined if LBP concentrations were associated with common polymorphisms in genes coding for LBP (rs2232618), CD14 (rs2569190), and TLR4 (rs4986790), the molecules responsible for the innate immune response to LPS, or serum levels of soluble CD14 (sCD14) and proinflammatory cytokines.MethodsSerum LBP was measured with a commercial immunoassay in a random sample of the adult population (n = 420, 45% males, age 18–92 years) from a single municipality.ResultsSerum LBP concentrations increased with age (P<0.001) and were higher in individuals who were overweight or obese than in normal-weight individuals (P<0.001). Similarly, LBP concentrations were higher in individuals with metabolic syndrome than in individuals without it (P<0.001). Among metabolic syndrome components, LBP concentrations were independently associated with abdominal obesity (P = 0.002) and low concentrations of HDL-cholesterol (P<0.001). Serum LBP concentrations tended to be independently associated with smoking (P = 0.05), but not with alcohol consumption. Likewise, there was not significant association between LBP concentrations and gene polymorphisms. Concentrations of LBP significantly correlated with serum levels of proinflammatory cytokines (IL-6 and IL-8), sCD14, and with liver enzymes.ConclusionsSerum LBP concentrations increased with age. Overweight, obesity, and having metabolic syndrome (particularly, low HDL cholesterol levels) were associated with higher LBP concentrations. These findings are consistent with microbial exposure playing a role in these inflammatory, metabolic abnormalities.
Highlights
A dysregulated response to bacteria or their products such as lipopolysaccharide (LPS, endotoxin) underlies many common inflammatory diseases [1,2]
Humans are equipped with an LPS-sensing machinery consisting primarily of LPS-binding protein (LBP); CD14, a glycosylphosphatidyl-inositol (GPI)-anchored monocyte differentiation antigen; and toll-like receptor 4 (TLR4), a signal-transducing integral membrane protein [2]
Membrane CD14 is associated with TLR4, which transduces a signal from the CD14-bound LPS to the cell nucleus, triggering a cascade of inflammatory cytokines [10]
Summary
A dysregulated response to bacteria or their products such as lipopolysaccharide (LPS, endotoxin) underlies many common inflammatory diseases [1,2]. Membrane CD14 is associated with TLR4, which transduces a signal from the CD14-bound LPS to the cell nucleus, triggering a cascade of inflammatory cytokines [10]. Some of these cytokines, IL-1 and IL-6, induce the synthesis of acute-phase proteins in the liver [11]. Assessment of serum concentration of lipopolysaccharide (LPS)-binding protein (LBP) has been suggested as a useful biomarker to indicate activation of innate immune responses to microbial products. We examined if LBP concentrations were associated with common polymorphisms in genes coding for LBP (rs2232618), CD14 (rs2569190), and TLR4 (rs4986790), the molecules responsible for the innate immune response to LPS, or serum levels of soluble CD14 (sCD14) and proinflammatory cytokines
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