Decreased toll-like receptor-4/myeloid differentiation factor 88 response leads to defective interleukin-1β production in term low birth weight newborns.

Abstract

BACKGROUND:

Morbidity and mortality rates are very high in low birth weight (LBW) newborns because of their increased susceptibility to infections compared with normal birth weight (NBW) newborns. A case and control study was designed to identify the status of toll-like receptor-4 (TLR-4) signaling and maternally derived immunoglobulin-G (IgG) subclasses in term LBW newborns compared with NBW newborns.

METHODS:

To understand the basis of increased susceptibility to infections in LBW newborns, the levels of pro- and antiinflammatory cytokines interleukin-1β (IL-1β) and interleukin-10 (IL-10), respectively, released in response to lipopolysaccharide (LPS) stimulation of cord blood cells of LBW (n = 20) and NBW (n = 18) newborns, were quantified by enzyme-linked immunosorbent assay. Further, LPS-induced expression of TLR-4 and basal and LPS-induced expression of myeloid differentiation factor 88 (MyD88) were examined at mRNA levels in both groups. The levels of IgG subclasses in LBW (n = 20) and NBW (n = 18) newborns were quantified by enzyme-linked immunosorbent assay to explore the role of maternally derived immunity in LBW newborns.

RESULTS:

LPS-mediated release of IL-1β was significantly diminished in LBW newborns when compared with NBW newborns, whereas there was no significant difference in IL-10. Decreased production of IL-1β in LBW newborns was correlated with reduced expression of TLR-4 and MyD88 mRNA. No significant differences were observed in the levels of all 4 IgG subclasses between LBW and NBW newborns.

CONCLUSIONS:

Decreased production of IL-1β in LBW newborns was correlated with reduced expression of TLR-4 and MyD88 mRNA. This raises the possibility of increased susceptibility to infections in LBW when compared with the NBW newborns at term. Comparable levels of IgG subclasses in the 2 groups of newborns indicate that IgG is not a limiting factor in defense against infection in LBW newborns.

• Authors: Vikas Vikram Singh, Sudhir Kumar Chauhan, Richa Rai, Ashok Kumar, Geeta Rai
• Journal: The Pediatric infectious disease journal (Pediatr Infect Dis J) Vol. 33 Issue 12 Pg. 1270-6 (Dec 2014) ISSN: 1532-0987 [Electronic] United States
• PMID: 25389708 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IL10 protein, human
• Immunoglobulin G
• Interleukin-1beta
• Lipopolysaccharides
• MYD88 protein, human
• Myeloid Differentiation Factor 88
• TLR4 protein, human
• Toll-Like Receptor 4
• Interleukin-10

Topics

• Communicable Diseases (immunology)
• Disease Susceptibility
• Enzyme-Linked Immunosorbent Assay
• Female
• Fetal Blood (immunology)
• Gene Expression Profiling
• Humans
• Immunity, Maternally-Acquired
• Immunoglobulin G (blood)
• Infant, Low Birth Weight
• Infant, Newborn
• Interleukin-10 (metabolism)
• Interleukin-1beta (metabolism)
• Leukocytes, Mononuclear (immunology)
• Lipopolysaccharides (immunology)
• Male
• Myeloid Differentiation Factor 88 (biosynthesis, genetics)
• Pregnancy
• Toll-Like Receptor 4 (biosynthesis, genetics)