Maternal care modulates the febrile response to lipopolysaccharide through differences in glucocorticoid receptor sensitivity in the rat

Brain Behav Immun. 2017 Oct;65:239-250. doi: 10.1016/j.bbi.2017.05.007. Epub 2017 May 10.

Abstract

Early life adversity increases the risk for later infection. The febrile response is a potent mechanism to combat infection. We found that variations in maternal care influence the febrile response to 50µg/kg lipopolysaccharide (LPS) challenge in adult male rats. Offspring from low-licking/grooming (LG) mothers had an increased febrile response compared to offspring from high-LG mothers challenged with LPS. Low-LG offspring had reduced plasma IL-6 at one and two hours post challenge compared to high-LG offspring. IL-6 gene expression in the anterior hypothalamus was induced following LPS challenge in low-LG offspring but not in high-LG offspring at two hours post challenge. Occupancy of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) to the IL-6 promoter region in the anterior hypothalamus was greater in low-LG offspring treated with LPS than in high-LG offspring. These findings suggest greater activation of thermoregulatory neurons in the anterior hypothalamus of low-LG compared to high-LG offspring following LPS challenge. Low-LG offspring had greater plasma corticosterone levels following LPS challenge and they had enhanced glucocorticoid receptors (GR) in the spleen compared to high-LG offspring. Enhanced glucocorticoids and glucocorticoid receptor sensitivity associated with reduced IL-6 induction early post challenge in low-LG offspring. Challenge with RU-486 prior to LPS challenge eliminated differences in the febrile response between offspring of high and low-LG mothers. Individual differences in GR sensitivity may modulate differences in the febrile response to LPS challenge, exerting a long-term influence on the capacity to recover from infection.

Keywords: Corticosterone; Febrile response; Glucocorticoid receptors; Interleukin-6; Maternal care; NFκB; RU-486 (mifepristone); Telemetry.

MeSH terms

  • Animals
  • Animals, Newborn
  • Behavior, Animal / physiology
  • Body Temperature / drug effects
  • Corticosterone / pharmacology
  • Female
  • Fever / chemically induced
  • Fever / metabolism
  • Fever / physiopathology*
  • Glucocorticoids / pharmacology
  • Lipopolysaccharides
  • Male
  • Maternal Behavior / physiology*
  • Neurons / drug effects
  • Rats
  • Rats, Long-Evans
  • Receptors, Glucocorticoid / metabolism*
  • Stress, Psychological

Substances

  • Glucocorticoids
  • Lipopolysaccharides
  • Receptors, Glucocorticoid
  • Corticosterone