Decreased toll-like receptor-4/myeloid differentiation factor 88 response leads to defective interleukin-1β production in term low birth weight newborns.
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.
From the *Department of Molecular and Human Genetics, Faculty of Science; and †Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Vikas Vikram
VV
Singh
Sudhir Kumar
SK
Chauhan
Richa
R
Rai
Ashok
A
Kumar
Geeta
G
Rai
D003141:Communicable Diseases / Q000276:immunology; D004198:Disease Susceptibility; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D007112:Immunity, Maternally-Acquired; D007074:Immunoglobulin G / Q000097:blood; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis* / Q000235:genetics; D011247:Pregnancy; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000235:genetics
C508609:IL10 protein, human; D007074:Immunoglobulin G; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D016753:Interleukin-10