Acute Illness is Associated with Suppression of the Growth Hormone Axis in Zimbabwean Infants

Abstract

Abstract. Frequent infections contribute to childhood stunting in developing countries but the causal pathways are uncertain. We tested the hypothesis that intercurrent illnesses suppress the growth hormone axis through reductions in insulin-like growth factor 1 (IGF-1). In a birth cohort of 202 HIV-unexposed Zimbabwean infants, we analyzed data on 7-day illness recall and measured plasma interleukin-6, C-reactive protein, alpha-1-acid glycoprotein, and IGF-1 by enzyme-linked immunosorbent assay, at age 6 weeks, and then 3, 6, 12, and 18 months. Children with recent acute illness had lower IGF-1 concentrations than healthy children and IGF-1 correlated inversely (P 0.05) with inflammatory biomarkers at most time points between 3 and 18 months. Using path analysis, we showed that cough and fever had a predominantly indirect effect on suppressing IGF-1, through the acute-phase response, whereas diarrhea had a predominantly direct effect on IGF-1. Acute illness may therefore impact the growth hormone axis through both direct and indirect pathways.

Increased postnatal concentrations of pro-inflammatory cytokines are associated with reduced IGF-I levels and retinopathy of prematurity

“…Two weeks of nutritional intervention resulted in a 3-fold increase in IGF-I and a 6-fold decrease in IL-6 [36]. Similarly, a negative correlation was found between plasma IGF-I levels and inflammation markers, including IL-6, in growth-stunted Zimbabwean children followed from 6 weeks of life [37]. Furthermore, in connection with infectious disease, low levels of IGF-I and elevated levels of inflammation markers have been reported, indicating that recent acute illness is associated with decreased IGF-I levels [37].…”

“…Similarly, a negative correlation was found between plasma IGF-I levels and inflammation markers, including IL-6, in growth-stunted Zimbabwean children followed from 6 weeks of life [37]. Furthermore, in connection with infectious disease, low levels of IGF-I and elevated levels of inflammation markers have been reported, indicating that recent acute illness is associated with decreased IGF-I levels [37]. Similar to starvation, infection and trauma in extremely preterm birth is associated with catabolism.…”

Systemic inflammation, growth factors, and linear growth in the setting of infection and malnutrition

“…Enteric infections involving poor growth have been linked to subclinical infections and may exhibit both systemic inflammation and elevations in stool inflammatory markers such as myeloperoxidase, α1 antitrypsin, and neopterin without overt diarrheal symptoms [8]. The presence of systemic inflammation during infection may play a role in growth suppression, as similar linear growth deficits have been noted in other conditions with high levels of systemic inflammation, such as Crohn's disease and juvenile idiopathic arthritis, in which poor growth is associated with high levels of inflammatory markers, low levels of important growth factors such as insulin-like growth factor (IGF)-1, and poor responsiveness of the growth plate [9], [10], [11], [12].…”

“…Links between infections, inflammatory markers such as C-reactive protein (CRP), and levels of IGF-1 recently have been demonstrated in a cohort of young children followed in Zimbabwe [10]. Similarly, a group of researchers in Uganda studied children presenting with severe acute malnutrition (mean weight-for-height Z scores of −4.2), reporting high levels of systemic inflammation and GH and low levels of IGF-1 [16].…”

Mice with infectious colitis exhibit linear growth failure and subsequent catch-up growth related to systemic inflammation and IGF-1

“…While diarrhea-related mortality has decreased over the past 20 years, morbidity persists, including nutritional deficits, and retardation of linear and ponderal growth [2]. The underlying mechanisms of poor linear growth in these settings remain unclear including whether the weight and height deficits are related to decreased food intake, systemic inflammation, poor absorption of nutrients, and dysregulation of systemic growth factors such as insulin-like growth factor (IGF)-1 [3, 4]. Persistent length/height measurement of more than two standard deviations below the mean (i.e., stunting) affects many of these children, even after resolution of the intestinal infections [5, 6].…”