Temporal Pattern and Effect of Sex on Lipopolysaccharide-Induced Stress Hormone and Cytokine Response in Pigs

Domest Anim Endocrinol. 2009 Oct;37(3):139-47. doi: 10.1016/j.domaniend.2009.04.004. Epub 2009 May 31.


The temporal pattern and sex effect of immune and stress hormone responses to a lipopolysaccharide (LPS) challenge were assessed using a pig model. Secretion of the pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 increased in a time-dependent manner following LPS infusion. There was also a time-dependent increase in secretion of the stress-related hormones cortisol, epinephrine (E), and norepinephrine (NE) following LPS, with peak concentrations attained within 30 min. The magnitude of the TNF-alpha and IL-1beta responses were both positively associated (P < 0.05) with the magnitude of cortisol response following LPS, whereas serum IL-1beta and IL-6 were positively correlated with the magnitude of E and NE responses following LPS. Acute-phase protein production was also time-dependently increased following LPS. The concentration of immune cells in circulation was decreased (P < 0.05) at 5.5h post-LPS and negatively correlated with pro-inflammatory cytokine production. By 24h post-LPS, immune cell counts increased (P < 0.05) and were positively associated with both pro-inflammatory cytokine and stress hormone production. The amplitude of pro-inflammatory cytokine response following LPS was affected (P < 0.05) by sex classification; however, the magnitude of elevated cytokine concentrations was not. The magnitude of the NE response, but not of the E and cortisol responses, to LPS was influenced by sex (P < 0.05). Similar to the pro-inflammatory cytokines, the magnitude of exposure to the stress hormones following LPS was not influenced by sex. The production of serum amyloid A (SAA) was influenced by sex, with barrows producing more SAA than gilts at 24h post-LPS (P < 0.05). Collectively, these results demonstrate sex-specific, concomitant temporal changes in innate immune- and stress-related hormones.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Epinephrine / blood
  • Epinephrine / immunology
  • Female
  • Hydrocortisone / blood
  • Hydrocortisone / immunology
  • Immunity, Innate / immunology
  • Interleukin-1beta / blood
  • Interleukin-1beta / immunology
  • Interleukin-6 / blood
  • Interleukin-6 / immunology
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / pharmacology*
  • Male
  • Norepinephrine / blood
  • Norepinephrine / immunology
  • Serum Amyloid A Protein / analysis
  • Serum Amyloid A Protein / immunology
  • Sex Factors
  • Stress, Physiological / immunology*
  • Swine / blood
  • Swine / immunology*
  • Time Factors
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / immunology


  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • Serum Amyloid A Protein
  • Tumor Necrosis Factor-alpha
  • Hydrocortisone
  • Norepinephrine
  • Epinephrine