ESPE Abstracts

Accumulating evidence indicates various interactions between the GH-IGF1 axis and the immune system in infants and children during undernutrition.

Objectives and Methods: We performed electronic literature systematic review using PubMed, Google Scholar, and Web of Sciences with the aim to provide an update on the link between the GH-IGF1 axis and the immune system in infants and children during malnutrition. We reviewed 22 studies (2007-2022) fitting the search criteria. 

Results: GH resistance and low IGF-I production appear to be adaptive mechanisms to preserve calories during malnutrition. Protein deficiency results in a state of GH resistance as well as a state of end-organ resistance to IGF-I. Zinc, magnesium, and vitamin B6 deficiencies that occur in many children with malnutrition have been associated with GH resistance and reduced IGF-I levels (Unknown mechanisms). GH and IGF-1 have important immunoregulatory effects. GH and IGF-1 can protect the host from infection by promoting the maturation of myeloid cells, and phagocyte migration, producing superoxide anions and cytokines, and enhancing opsonic activity. Moreover, IGF-I plays an essential role in the growth, stimulation, proliferation, and function of T cells. IGF-I regulates various aspects of T-cell, B-cell, and monocyte function through its interactions with IGF-IR. IGF-I can prolong lymphocyte survival through the activation of T cell Akt. IGFs depress proinflammatory cytokine signaling by increasing IL-10 secretion via JNK and NF-κB pathways. On the other hand, pro-inflammatory cytokines, which increase in severe forms of malnutrition especially those with infection, induce a dysregulation in GH–IGF axis and IGF system, both at central and peripheral levels. In the liver, TNF-α, a pro-inflammatory cytokine can cause GH resistance mainly through the downregulation of liver GH receptor expression. Additionally, the predominance of proinflammatory cytokines decreases IGF sensitivity by enhancing IGFBP production and by decreasing signaling through the (insulin receptor signaling) IRS/ Akt pathway. The increase in local muscle cytokines produced during infections makes the muscle GH-resistant and reduces its own IGF-I production, leading to muscle wasting. Myokines secreted by the skeletal muscle in response to inflammation mediate wasting. A randomized controlled using the anti-inflammatory drug “mesalazine” treatment for 56 days in acutely undernourished children with enteric dysfunction increased IGF-1 levels and decreased the inflammatory markers with improving linear growth.

Conclusion: During malnutrition IGF1 deficiency and GH resistance can negatively affect the functions of the immune system (lymphocytes and cytokines) and predispose to infection and inflammation which further deteriorate growth and induce wasting.