Decreased anti-inflammatory responses to vitamin D in neonatal neutrophils

Daniel Hirsch1, Faith E Archer, Meera Joshi-Kale

  • 1Division of Neonatology, Department of Pediatrics, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08901, USA.

Insights

Vitamin D (1,25-dihydroxyvitamin D3) normally suppresses neutrophil activation, but this anti-inflammatory effect is impaired in newborns due to reduced vitamin D receptor expression, potentially contributing to neonatal inflammation.

Area of Science:

  • Immunology
  • Neonatal Medicine
  • Endocrinology

Background:

  • Neutrophil activity is prolonged in newborns.
  • This suggests reduced responses to immunosuppressive factors like 1,25-dihydroxyvitamin D3 (1,25-vit D3).

Purpose of the Study:

  • To investigate if 1,25-vit D3 suppresses neutrophil activation.
  • To determine if this response is impaired in neonatal neutrophils.

Main Methods:

  • Compared 1,25-vit D3 effects on lipopolysaccharide (LPS)-induced neutrophil activation in adult and neonatal cells.
  • Measured expression of vitamin D receptor (VDR) and 1α-hydroxylase in neutrophils.
  • Assessed inflammatory mediator and enzyme expression (MIP-1β, VEGF, COX-2, 5-LOX).

Main Results:

  • 1,25-vit D3 decreased inflammatory markers in adult neutrophils but not neonatal ones.
  • Neonatal neutrophils showed reduced VDR and 1α-hydroxylase expression.
  • 1,25-vit D3 induced VDR expression in adult neutrophils, but not neonatal.
  • Vitamin D insensitivity did not affect respiratory burst in either group.

Conclusions:

  • Neonatal neutrophils exhibit impaired anti-inflammatory responses to 1,25-vit D3.
  • Reduced VDR and 1α-hydroxylase expression likely underlies this insensitivity.
  • This neonatal vitamin D insensitivity may contribute to chronic inflammation.

Related Concept Videos

Role of Skin in Vitamin D Synthesis01:23

Role of Skin in Vitamin D Synthesis

The skin plays a crucial role in the synthesis of vitamin D, a vital nutrient for various physiological processes in the body. Vitamin D is unique because it can be synthesized in the skin through a series of chemical reactions triggered by exposure to ultraviolet B (UVB) radiation from sunlight.
The solar UV B rays (290-315 nm) are absorbed by the skin, and 7-dehydrocholesterol (provitamin D3) photolyzes it to previtamin D3, which undergoes a rapid transformation to vitamin D3(cholecalciferol).
Development of Immunocompetence01:22

Development of Immunocompetence

The initiation of cell-mediated immunity can be observed as early as the third month of fetal growth, with active antibody-mediated immunity following approximately one month later.
The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.
Subsequent T...
Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption01:23

Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption

Understanding the physiological differences in the pediatric population is crucial for effective pharmacotherapy. Neonates, infants, and children exhibit significant variations in gastric pH, gastric emptying time, intestinal transit time, and biliary function. These variations profoundly affect oral drug absorption, necessitating a nuanced approach to pediatric dosing.Neonates present with a unique physiological profile, having a gastric pH greater than 4 and faster and more irregular gastric...
Pharmacokinetics in Pediatric Patients: Drug Distribution01:17

Pharmacokinetics in Pediatric Patients: Drug Distribution

Drug distribution in the pediatric population exhibits unique challenges and considerations due to the physiological differences between children, particularly neonates and infants, and adults. A crucial aspect of pediatric pharmacology is understanding how these differences impact the pharmacokinetics of various drugs, necessitating age-specific dosing strategies to ensure efficacy and safety.Neonates and infants have a higher total body water content, ~75%–90% of their body weight, compared...
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...