Modulation of the acute phase response by altered expression of the IL-1 type 1 receptor or IL-1ra

Am J Physiol Regul Integr Comp Physiol. 2000 Apr;278(4):R824-30. doi: 10.1152/ajpregu.2000.278.4.R824.


A complete understanding of the role for endogenously produced interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and IL-1 receptor antagonist (IL-1ra) in the acute phase response to inflammation remains unknown. In the present studies, knockout mice lacking either a functional IL-1 type I receptor (IL-1RI(-/-)), a TNF type I receptor (TNFR-I(-/-)), or both IL-1 type I and TNF type I receptors (IL-1RI(-/-)/TNFR-I(-/-)) received a turpentine abscess. Additional mice deficient in IL-1ra protein (IL-1ra(-/-)) or overexpressing IL-1ra protein (IL-1ra(tg)) were similarly treated. After a turpentine abscess, IL-1 receptor knockout mice exhibited an attenuated inflammatory response compared with wild-type or animals lacking a functional TNFR-I. Mice overexpressing IL-1ra also had an attenuated hepatic acute phase protein response, whereas IL-1ra knockout mice had a significantly greater hepatic acute phase response. We conclude that the inflammatory response to a turpentine abscess is the result of a balance between IL-1ra expression and IL-1 binding to its type I receptor. Endogenously produced IL-1ra plays a central role in mitigating the magnitude of the IL-1-mediated inflammatory response and, ultimately, the outcome to a turpentine abscess.

Publication types

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

MeSH terms

  • Abscess / chemically induced
  • Abscess / immunology
  • Abscess / physiopathology
  • Acute-Phase Reaction / genetics*
  • Acute-Phase Reaction / immunology*
  • Animals
  • Anorexia / immunology
  • Anorexia / physiopathology
  • Appetite / immunology
  • Body Weight
  • Cachexia / immunology
  • Cachexia / physiopathology
  • Eating
  • Female
  • Gene Expression / immunology
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-6 / immunology
  • Irritants
  • Liver / immunology
  • Liver / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Knockout
  • Receptors, Interleukin-1 / genetics*
  • Receptors, Tumor Necrosis Factor / immunology
  • Sialoglycoproteins / genetics*
  • Signal Transduction / immunology
  • Tumor Necrosis Factor-alpha / immunology
  • Turpentine


  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-6
  • Irritants
  • Receptors, Interleukin-1
  • Receptors, Tumor Necrosis Factor
  • Sialoglycoproteins
  • Tumor Necrosis Factor-alpha
  • Turpentine