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

Abstract

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.

• Authors: M D Josephs, C C Solorzano, M Taylor, J J Rosenberg, D Topping, A Abouhamze, S L Mackay, E Hirsch, D Hirsh, M Labow, L L Moldawer
• Journal: American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 278 Issue 4 Pg. R824-30 (Apr 2000) ISSN: 0363-6119 [Print] United States
• PMID: 10749768 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

• Abscess (chemically induced, immunology, physiopathology)
• Acute-Phase Reaction (genetics, immunology)
• Animals
• Anorexia (immunology, physiopathology)
• Appetite (immunology)
• Body Weight
• Cachexia (immunology, physiopathology)
• Eating
• Female
• Gene Expression (immunology)
• Interleukin 1 Receptor Antagonist Protein
• Interleukin-6 (immunology)
• Irritants
• Liver (immunology, 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