PMID- 25389708 OWN - NLM STAT- MEDLINE DCOM- 20150626 LR - 20181202 IS - 1532-0987 (Electronic) IS - 0891-3668 (Linking) VI - 33 IP - 12 DP - 2014 Dec TI - Decreased toll-like receptor-4/myeloid differentiation factor 88 response leads to defective interleukin-1beta production in term low birth weight newborns. PG - 1270-6 LID - 10.1097/INF.0000000000000416 [doi] AB - 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-1beta (IL-1beta) 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-1beta was significantly diminished in LBW newborns when compared with NBW newborns, whereas there was no significant difference in IL-10. Decreased production of IL-1beta 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-1beta 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. FAU - Singh, Vikas Vikram AU - Singh VV AD - From the *Department of Molecular and Human Genetics, Faculty of Science; and daggerDepartment of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. FAU - Chauhan, Sudhir Kumar AU - Chauhan SK FAU - Rai, Richa AU - Rai R FAU - Kumar, Ashok AU - Kumar A FAU - Rai, Geeta AU - Rai G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Pediatr Infect Dis J JT - The Pediatric infectious disease journal JID - 8701858 RN - 0 (IL10 protein, human) RN - 0 (Immunoglobulin G) RN - 0 (Interleukin-1beta) RN - 0 (Lipopolysaccharides) RN - 0 (MYD88 protein, human) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Communicable Diseases/immunology MH - Disease Susceptibility MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Fetal Blood/immunology MH - Gene Expression Profiling MH - Humans MH - Immunity, Maternally-Acquired MH - Immunoglobulin G/blood MH - *Infant, Low Birth Weight MH - Infant, Newborn MH - Interleukin-10/metabolism MH - Interleukin-1beta/*metabolism MH - Leukocytes, Mononuclear/immunology MH - Lipopolysaccharides/immunology MH - Male MH - Myeloid Differentiation Factor 88/*biosynthesis/genetics MH - Pregnancy MH - Toll-Like Receptor 4/*biosynthesis/genetics EDAT- 2014/11/13 06:00 MHDA- 2015/06/27 06:00 CRDT- 2014/11/13 06:00 PHST- 2014/11/13 06:00 [entrez] PHST- 2014/11/13 06:00 [pubmed] PHST- 2015/06/27 06:00 [medline] AID - 00006454-201412000-00015 [pii] AID - 10.1097/INF.0000000000000416 [doi] PST - ppublish SO - Pediatr Infect Dis J. 2014 Dec;33(12):1270-6. doi: 10.1097/INF.0000000000000416.