Leukocytes from wheezing infants release lower amounts of IL-12 and IFN-γ compared to non-wheezing infants

Angela Falcai1, Paulo Vítor Soeiro Pereira, Christina Arslanian Kubo

  • 1Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo-SP, Brazil.

Insights

Early life endotoxin exposure did not predict wheezing in infants. However, recurrent wheezing infants with higher endotoxin exposure showed reduced IL-12 and IFN-γ cytokine production.

Area of Science:

  • Environmental health
  • Immunology
  • Pediatric allergy

Background:

  • Early life environmental exposures, including endotoxin, are critical in immune system development.
  • Sensitization to aeroallergens and subsequent allergic diseases like asthma are significant concerns in high-risk infants.
  • Understanding the interplay between endotoxin, immune responses, and wheezing phenotypes is crucial for prevention strategies.

Purpose of the Study:

  • To investigate the relationship between early-life environmental endotoxin exposure and the development of wheezing.
  • To examine aeroallergen sensitization, cytokine production by leukocytes, and wheezing phenotypes in a high-risk infant cohort.
  • To determine if endotoxin exposure influences immune responses in infants who develop recurrent wheezing.

Main Methods:

  • Prospective cohort study of 84 high-risk infants from birth to 30 months.
  • Assessed house dust endotoxin levels in the first 6 months of life.
  • Evaluated wheezing, skin prick tests, and cytokine release (IL-12, IFN-γ, TNF-α, IL-10, IL-4, IL-5, IL17) from LPS-stimulated peripheral blood mononuclear cells (PBMC) at 30 months.

Main Results:

  • No association found between early endotoxin exposure and wheezing phenotype development.
  • Recurrent wheezing (RW) infants experienced a higher incidence of respiratory infections.
  • PBMC from RW infants exposed to higher endotoxin levels ( > 50 EU/mg) produced less IL-12p70 and IFN-γ compared to non-RW infants.
  • Production of TNF-α, IL-10, IL-4, IL-5, and IL17 was similar between RW and non-RW groups regardless of endotoxin exposure.

Conclusions:

  • Early-life endotoxin exposure levels were similar in recurrent wheezing (RW) and non-RW infants.
  • RW infants exposed to higher endotoxin levels showed significantly reduced IL-12 and IFN-γ production from LPS-stimulated PBMC.
  • These findings suggest a potential immunomodulatory role of endotoxin in the development of wheezing phenotypes, specifically affecting Th1-type responses.
Abstract

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