Acute inflammation in young children inhibits C-type natriuretic peptide

Abstract

Background: C-type natriuretic peptide (CNP) is a paracrine growth factor critical in endochondral bone growth. Amino-terminal CNP (NTproCNP), measurable in plasma, correlates with growth-plate activity and can be used as a biomarker of growth velocity in children. Because severe inflammation in adults increases CNP, we studied CNP peptides and inflammatory markers in children with acute illness. Methods: Forty-two children aged 2 mo to 5 y with acute illness warranting admission to an acute assessment unit were studied. Fifteen age-matched healthy children attending an outpatient clinic served as controls. Venous CNP concentrations were measured at admission, along with markers of acute inflammation (body temperature, C-reactive protein (CRP), and white blood cell count) in children with acute illness. results: NTproCNP and CNP SD scores (SDSs) in the acutely ill group were significantly suppressed (P < 0.001) as compared with those of healthy children or healthy population norms. NTproCNP SDS was significantly inversely related to body temperature (r = −0.42, P < 0.01) and CRP (r = −0.56, P < 0.001). conclusion: Acute inflammation in young children potently reduces CNP production, which needs to be considered when screening for growth disorders. Our data raise the possibility that the adverse effects of inflammatory cytokines on skeletal growth may be mediated in part by reduced CNP. c -type natriuretic peptide (CNP) is expressed in a wide range of tissues (1), but its regulation in vivo has been difficult to study because only small amounts of the active peptide enter the circulation. However, recognition that an inactive amino-terminal fragment of proCNP (NTproCNP) is co-secreted with CNP (2,3), is readily measured in plasma, and correlates with tissue CNP production (4), has opened the door to clinical studies-for example, study of changing CNP production during growth and development.In keeping with evidence showing that an intact CNP signaling pathway is crucial to postnatal endochondral growth (5,6), there is now strong support for the view that plasma concentrations of NTproCNP reflect concurrent linear growth velocity during childhood (3,7,8). Recent studies indicate that plasma NTproCNP concentration accounts for at least 50% of the variation in growth velocity in healthy children aged 2 mo to 20 y (9). Furthermore, changes in growth velocity initiated by hormone therapy (10) or glucocorticoid drugs (11) are closely correlated with concordant changes in plasma NTproCNP. Together, these findings suggest that, provided other pathophysiological variables are controlled, this peptide may be a useful marker of concurrent growth velocity. During the course of determining a provisional reference range for plasma CNP forms, we observed unusually low concentrations in very young children with intercurrent infections. This finding-unexpected in light of reports in adults showing that plasma CNP forms were raised in acute sepsis-raised the possibility that the CNP response to acute inflammation may differ in gro...

Role of C-type natriuretic peptide signalling in maintaining cartilage and bone function

“…In the only study which examined the effect of IL-1b on natriuretic peptide receptors in chondrocytes treated with CNP, the cytokine was reported to increase CNP levels and Npr3 expression, thereby augmenting potential beneficial effects mediated by Npr signalling 40 . In general, inflammation was previously shown to upregulate CNP levels but in children, peptide levels were found to be reduced 53 , presenting potential complications on growth relevant to young patients with Juvenile Idiopathic Arthritis (JIA). Since there is strong evidence for a role of endogenous CNP signalling in normal cartilage development, the potential therapeutic role for exogenous CNP in the treatment of skeletal growth disorders should be investigated further.…”

C-type natriuretic peptide and its contribution to bone growth

“…It is not about chronic diseases or chronic conditions are known to slow down growth, but also about acute and short-term illnesses. Prickett et al, investigating the concentration of NTproCNP and CNP in pre-school children with acute infection, have shown that the concentrations of both indicators are reduced, which suggests that the infection can slow down bone growth clinically unnoticeably [37]. Topçu et al investigated the NT-proCNP plasma concentration in the overweight or obese, in comparison to normal weight children.…”

Plasma C-Type Natriuretic Peptide: Emerging Applications in Disorders of Skeletal Growth

“…The obvious signs and symptoms of these diseases make their presence unlikely to confound interpretation. However, acute inflammation, which appears to lower NTproCNP in young children [45], could be overlooked in some settings. Reports of lower levels of CNP products in obese adolescents [46, 47] have not been supported by a more formal study where the crucial impact of age (and therefore height velocity) was taken into account [30].…”