Intrauterine growth restriction leads to a high-corticosterone producing offspring: An implication for pulmonary infection susceptibility

Author(s)

Gil, Noemi L. ^[1] ; Azevedo, Gabriela A. ^[1] ; Balbino, Aleksandro M. ^[1] ; Silva, Marina M. ^[1] ; Carvalho, Maria Helena C. ^[2] ; Akamine, Eliana H. ^[2] ; Keller, Alexandre C. ^[3] ; Landgraf, Richardt G. ^[1] ; Landgraf, Maristella A. ^[4]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Pharmaceut Sci, Campus Diadema, Rua Sao Nicolau 210, BR-09913030 Diadema, SP - Brazil

^[2] Univ Sao Paulo, Dept Pharmacol, Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil

^[4] Univ Paulista, Campus Rangel, Santos, SP - Brazil

• Document type: Journal article
• Source: Life Sciences; v. 281, SEP 15 2021.
• Web of Science Citations: 0

Abstract

Aims: Although intrauterine growth restriction (IUGR) impairs immune system homeostasis and lung development, its relationship with the susceptibility to pulmonary infections remains unclear. Thus, this study aimed to investigate the impact of IUGR on acute lung inflammatory response induced by bacterial stimulus. Materials and methods: Pregnant female Wistar rats were subjected to 50% caloric-protein food restriction during gestation. To mimic bacterial lung infection, adult male offspring (12 weeks old) were challenged with a single lipopolysaccharide (LPS) intranasal instillation, and 6 h later, we assessed the acute inflammatory response. Normal birth weight (NBW) animals represent the control group. Key findings: LPS instillation increased the protein levels in the airways of both the NBW and low birth weight (LBW) groups, indicating vascular leakage. LBW animals exhibited a lower number of neutrophils, reduced production of interleukin-6 and macrophage-inflammatory protein-2 and decreased upregulation of intercellular adhesion molecule-1 gene expression in lung tissues. Further analysis revealed that the LBW group produced lower levels of prostaglandin-E2 and failed to secrete leukotriene-B4 upon LPS stimulation, which correlated with impaired cyclooxygenase-2 and 5-lipoxygenase expression. These results were probably associated with their inability to upregulate the expression of Toll-like receptor-4 and downstream signaling proteins, such as nuclear factor kappa-B, in the lungs. The LBW group also exhibited abnormal airway thickening and high corticosterone levels under basal conditions. Significance: This study suggests that IUGR-induced foetal programming in LBW offspring threatens HPA axis physiology and corticosterone biodisponibility, and impairs the innate response to bacterial antigens, increasing future susceptibility to pulmonary infection. (AU)

• FAPESP's process: 19/11490-5 - The role of the sympathetic nervous system on the biological activity of invariant natural killer T lymphocytes
• Grantee: Alexandre de Castro Keller
• Support Opportunities: Regular Research Grants