NAMPT serum levels are selectively elevated in acute infectious disease and in acute relapse of chronic inflammatory diseases in children

Abstract

Nicotinamide phosphoribosyl transferase (NAMPT) is an inflammatory adipocytokine shown to interact in immune modulation in chronic inflammatory diseases, acute respiratory distress syndrome, sepsis, cancer and obesity in adulthood. It is, however, not clear whether this association reflects a chronic elevation or acute inflammatory response. We analyzed NAMPT concentrations in distinct states of inflammation in 102 children and found consistently significantly increased NAMPT levels in subjects with acute infections. NAMPT concentrations in children with stable chronic inflammatory diseases were not significantly different, whereas in patients with acute relapse of chronic disease NAMPT was significantly higher than in children in remission or healthy controls. In states of low-grade inflammation (children with atopic disease or obesity) we did not detect alterations in NAMPT serum levels. NAMPT correlated positively with inflammatory markers such as CRP. The most predictive factor for NAMPT serum concentrations was leucocyte count and therein the neutrophil count. Furthermore, systemic circulating NAMPT levels were closely associated with NAMPT release from corresponding cultured PBMCs. In conclusion, NAMPT is selectively increased in states of acute but not chronic inflammation in children. The close relationship between systemic circulating NAMPT with leucocyte counts and release indicate that leucocytes most probably are the source of inflammation related NAMPT levels.

Fig 1. NAMPT serum concentrations in distinct inflammatory conditions.

Comparison of NAMPT concentrations between patient groups of distinct inflammatory conditions and controls (A). Patients with chronic inflammation were further stratified into patients with active disease vs. patients without symptoms (remission) (B). Boxes are interquartile range, whiskers are minimum to maximum. Statistical significance was assessed by ANOVA and Tukey HSD test in log transformed values.

Fig 2. Positive correlation between NAMPT serum levels and inflammatory markers.

Correlation between log NAMPT serum concentration and log C-reactive protein (A), log ESR (1 hour) (B), log leucocyte count(C) and log neutrophil granulocyte count (D).

Fig 3. NAMPT release from PBMCs.

Comparison of NAMPT release between patient groups of distinct inflammatory conditions and controls (A). Boxes are interquartile range, whiskers are minimum to maximum. Statistical significance was assessed by ANOVA and Tukey HSD test. Correlation between log NAMPT serum concentrations and corresponding NAMPT release from PBMCs of the same patient (B) and Correlation between NAMPT release from PBMCs with blood neutrophil counts (C).