Circulating Cathelicidin Concentrations in a Cohort of Healthy Children: Influence of Age, Body Composition, Gender and Vitamin D Status

Abstract

Cathelicidin is an antimicrobial peptide whose circulating levels are related to vitamin D status in adults. This study sought to determine if circulating cathelicidin concentrations in healthy children are related to the age of the child, body composition and vitamin D status at birth and at the time of the study visit. Blood samples were obtained during yearly visits from 133 children, ages 2–7, whose mothers had participated in a pregnancy vitamin D supplementation RCT. Radioimmunoassay and ELISA were performed to analyze 25(OH)D and cathelicidin, respectively. Statistical analyses compared cathelicidin concentrations with concentrations of 25(OH)D at various time points (maternal levels throughout pregnancy, at birth, and child’s current level); and with race/ethnicity, age, gender, BMI, percent fat, and frequency of infections using Student’s t-test, χ2, Wilcoxon ranked-sum analysis, and multivariate regression. The cohort’s median cathelicidin concentration was 28.1 ng/mL (range: 5.6–3368.6) and did not correlate with 25(OH)D, but was positively correlated with advancing age (ρ = 0.236 & p = 0.005, respectively). Forty patients evaluated at two visits showed an increase of 24.0 ng/mL in cathelicidin from the first visit to the next (p<0.0001). Increased age and male gender were correlated with increased cathelicidin when controlling for race/ethnicity, percent fat, and child’s current 25(OH)D concentration (p = 0.028 & p = 0.047, respectively). This study demonstrated that as children age, the concentration of cathelicidin increases. Furthermore, male gender was significantly associated with increased cathelicidin concentrations. The lack of association between vitamin D status and cathelicidin in this study may be due to the narrow range in observed 25(OH)D values and warrants additional studies for further observation.

Association of vitamin D with cathelicidin and vitamin D binding protein in pediatric sepsis

“…The high prevalence of low 25(OH) D levels in septic children in our study is similar to previous reports suggesting a role for vitamin D in sepsis and immunity that warrants further exploration [4] , [6] , [12] . Interestingly, in our cohort, cathelicidin levels were three times that of healthy children in a previous report suggesting its importance in the initial immune response to infections [13] . However unlike adult studies, we did not find a correlation between vitamin D and cathelicidin levels.…”

Association between vitamin D, antimicrobial peptides and urinary tract infection in infants and young children

“…Interestingly, vitamin D, cathelicidin and β‐defensin‐2 negatively correlated with children's age with younger children having the highest levels. In children over three years of age, the levels seem to increase again . If we draw parallels with other epithelial surfaces , the innate immunity in form of AMPs, supported with adequate levels of vitamin D, may be of a crucial importance early in life, where the adaptive immune system is still building up.…”

Vitamin D Supplementation Guidelines for General Population and Groups at Risk of Vitamin D Deficiency in Poland—Recommendations of the Polish Society of Pediatric Endocrinology and Diabetes and the Expert Panel With Participation of National Specialist Consultants and Representatives of Scientific Societies—2018 Update

“…It has been reported that calcitriol takes part in numerous physiological processes, including enhancement of proliferation and differentiation of immune cells ( 52 , 53 ). It induces apoptosis of neoplastic cells and inhibits their multiplication ( 52 , 53 ), increases production of cathelicidin and beta-defensin ( 51 , 54 – 56 ), modulates lymphocyte activity ( 51 ), Th1 and Th2 lymphocyte ratio ( 51 , 57 ), decreases concentrations of proinflammatory cytokines (IL-1, TNFα), simultaneously increasing anti-inflammatory cytokines (IL-4, IL-5 and IL-10) ( 51 , 58 ), decreases renin secretion and in this way reduces activity of the renin–angiotensin–aldosteron system ( 59 , 60 ), inhibits angiogenesis ( 61 – 63 ), and has favorable effect on calcification processes in blood vessels ( 64 – 67 ), stimulates synthesis of neurotrophic factors ( 68 , 69 ) and inhibits fibrosis in kidneys ( 70 , 71 ). Vitamin D deficiency decreases insulin secretion ( 72 ).…”