Testosterone and IL-6 requirements for human C-reactive protein gene expression in transgenic mice

J Immunol. 1998 Jun 1;160(11):5294-9.


In vitro, IL-6 is the main inducer of the human C-reactive protein (CRP) gene, and IL-1 and steroids can enhance this effect. However, in mice, IL-6 is necessary but not sufficient for induction of the human CRP transgene, and testosterone is required for its constitutive expression by males. To examine the relative contributions of testosterone and IL-6 in the regulation of CRP gene expression, we produced CRP-transgenic (CRPtg), IL-6-deficient (IL-6-/-) mice. Male CRPtg/IL-6-/- mice expressed CRP constitutively, but CRP levels were not increased after injection of LPS. However, acute-phase CRP levels were attained after injection of IL-6. In contrast, female CRPtg/IL-6-/- mice did not express CRP constitutively or after administration of LPS, IL-6, IL-1, or IL-6 plus IL-1. Like males, testosterone-treated CRPtg/IL-6-/- females expressed CRP constitutively, and their transgene responded to injection of IL-6. The endogenous acute-phase protein serum amyloid P (SAP) was expressed constitutively equally by male and female IL-6-/- mice, responded minimally to LPS, and did not respond to either IL-6 or IL-1 alone. Acute-phase levels of SAP were induced in IL-6-/- mice by injection of IL-6 together with IL-1 or LPS. We conclude that in vivo, both constitutive and IL-6-dependent acute-phase expression of the CRP transgene require testosterone. In contrast, testosterone is not required for expression of the SAP gene, which requires IL-1 plus IL-6 for acute-phase induction.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Animals
  • C-Reactive Protein / biosynthesis
  • C-Reactive Protein / genetics*
  • C-Reactive Protein / metabolism
  • Drug Combinations
  • Female
  • Gene Expression Regulation / immunology*
  • Humans
  • Injections, Intraperitoneal
  • Interleukin-1 / administration & dosage
  • Interleukin-6 / administration & dosage
  • Interleukin-6 / physiology*
  • Lipopolysaccharides / administration & dosage
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Serum Amyloid P-Component / biosynthesis
  • Sex Factors
  • Testosterone / administration & dosage
  • Testosterone / physiology*
  • Transgenes / immunology


  • Drug Combinations
  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharides
  • Serum Amyloid P-Component
  • Testosterone
  • C-Reactive Protein