Abstract
A specific interleukin-1 (IL-1) receptor antagonist (IL-1ra) was used to examine the roles of IL-1 in an experimental model designed to analyze the reactivation phase of erosive arthritis, induced in rats with peptidoglycan-polysaccharide polymers (PG-APS) isolated from cell walls of group A streptococci. Monoarticular arthritis was initiated by injection of a small dose of PG-APS into an ankle joint, and reactivation was induced by intravenous injection of PG-APS 20 days later. Human recombinant IL-1ra given at a dose of 2 to 3 mg/kg at the time of reactivation of arthritis and at 6-h intervals inhibits the increase in joint swelling by at least 60%. Joint swelling is suppressed 30 to 50% when the initial treatment with IL-1ra is delayed until 6 h after reactivation. IL-1ra is not effective when the initial injection is delayed 12 or 24 h. With an injection schedule of IL-1ra given at the time of reactivation and every 6 h, treatment can be stopped at 24 h and the suppression of swelling is no different from that in rats for which injections are continued for 4 days. The results indicate that IL-1 has a prominent, although not exclusive, role in initiating inflammation in this model and is involved in the amplifying processes in progressive inflammation and chronic erosive disease. An anti-inflammatory function of IL-1 is also indicated from data showing that IL-1ra treatment limited to 6 h or less after the induction of reactivation enhances joint swelling, whereas intravenous injection of human recombinant IL-1 beta 24 h before reactivation suppresses the reactivation of arthritis.
Full text
PDF![4436](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6359/259060/2f099c39c7da/iai00048-0156.png)
![4437](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6359/259060/51680f516dbc/iai00048-0157.png)
![4438](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6359/259060/a1e0f3d00ff1/iai00048-0158.png)
![4439](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6359/259060/813d51bd21f2/iai00048-0159.png)
![4440](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6359/259060/57c4c2fceaad/iai00048-0160.png)
![4441](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6359/259060/df6dc8ee6b02/iai00048-0161.png)
![4442](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6359/259060/735682520fca/iai00048-0162.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arend W. P., Joslin F. G., Thompson R. C., Hannum C. H. An IL-1 inhibitor from human monocytes. Production and characterization of biologic properties. J Immunol. 1989 Sep 15;143(6):1851–1858. [PubMed] [Google Scholar]
- Arend W. P., Welgus H. G., Thompson R. C., Eisenberg S. P. Biological properties of recombinant human monocyte-derived interleukin 1 receptor antagonist. J Clin Invest. 1990 May;85(5):1694–1697. doi: 10.1172/JCI114622. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bomsztyk K., Sims J. E., Stanton T. H., Slack J., McMahan C. J., Valentine M. A., Dower S. K. Evidence for different interleukin 1 receptors in murine B- and T-cell lines. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8034–8038. doi: 10.1073/pnas.86.20.8034. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carter D. B., Deibel M. R., Jr, Dunn C. J., Tomich C. S., Laborde A. L., Slightom J. L., Berger A. E., Bienkowski M. J., Sun F. F., McEwan R. N. Purification, cloning, expression and biological characterization of an interleukin-1 receptor antagonist protein. Nature. 1990 Apr 12;344(6267):633–638. doi: 10.1038/344633a0. [DOI] [PubMed] [Google Scholar]
- Chizzonite R., Truitt T., Kilian P. L., Stern A. S., Nunes P., Parker K. P., Kaffka K. L., Chua A. O., Lugg D. K., Gubler U. Two high-affinity interleukin 1 receptors represent separate gene products. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8029–8033. doi: 10.1073/pnas.86.20.8029. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clark R. L., Cuttino J. T., Jr, Anderle S. K., Cromartie W. J., Schwab J. H. Radiologic analysis of arthritis in rats after systemic injection of streptococcal cell walls. Arthritis Rheum. 1979 Jan;22(1):25–35. doi: 10.1002/art.1780220105. [DOI] [PubMed] [Google Scholar]
- Cominelli F., Nast C. C., Llerena R., Dinarello C. A., Zipser R. D. Interleukin 1 suppresses inflammation in rabbit colitis. Mediation by endogenous prostaglandins. J Clin Invest. 1990 Feb;85(2):582–586. doi: 10.1172/JCI114476. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cromartie W. J., Craddock J. G., Schwab J. H., Anderle S. K., Yang C. H. Arthritis in rats after systemic injection of streptococcal cells or cell walls. J Exp Med. 1977 Dec 1;146(6):1585–1602. doi: 10.1084/jem.146.6.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dalldorf F. G., Cromartie W. J., Anderle S. K., Clark R. L., Schwab J. H. The relation of experimental arthritis to the distribution of streptococcal cell wall fragments. Am J Pathol. 1980 Aug;100(2):383–402. [PMC free article] [PubMed] [Google Scholar]
- Eastgate J. A., Symons J. A., Wood N. C., Grinlinton F. M., di Giovine F. S., Duff G. W. Correlation of plasma interleukin 1 levels with disease activity in rheumatoid arthritis. Lancet. 1988 Sep 24;2(8613):706–709. doi: 10.1016/s0140-6736(88)90185-7. [DOI] [PubMed] [Google Scholar]
- Eisenberg S. P., Evans R. J., Arend W. P., Verderber E., Brewer M. T., Hannum C. H., Thompson R. C. Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist. Nature. 1990 Jan 25;343(6256):341–346. doi: 10.1038/343341a0. [DOI] [PubMed] [Google Scholar]
- Esser R. E., Anderle S. K., Chetty C., Stimpson S. A., Cromartie W. J., Schwab J. H. Comparison of inflammatory reactions induced by intraarticular injection of bacterial cell wall polymers. Am J Pathol. 1986 Feb;122(2):323–334. [PMC free article] [PubMed] [Google Scholar]
- Esser R. E., Stimpson S. A., Cromartie W. J., Schwab J. H. Reactivation of streptococcal cell wall-induced arthritis by homologous and heterologous cell wall polymers. Arthritis Rheum. 1985 Dec;28(12):1402–1411. doi: 10.1002/art.1780281213. [DOI] [PubMed] [Google Scholar]
- Hannum C. H., Wilcox C. J., Arend W. P., Joslin F. G., Dripps D. J., Heimdal P. L., Armes L. G., Sommer A., Eisenberg S. P., Thompson R. C. Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature. 1990 Jan 25;343(6256):336–340. doi: 10.1038/343336a0. [DOI] [PubMed] [Google Scholar]
- Jacobs C., Young D., Tyler S., Callis G., Gillis S., Conlon P. J. In vivo treatment with IL-1 reduces the severity and duration of antigen-induced arthritis in rats. J Immunol. 1988 Nov 1;141(9):2967–2974. [PubMed] [Google Scholar]
- Ohlsson K., Björk P., Bergenfeldt M., Hageman R., Thompson R. C. Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature. 1990 Dec 6;348(6301):550–552. doi: 10.1038/348550a0. [DOI] [PubMed] [Google Scholar]
- Pettipher E. R., Higgs G. A., Henderson B. Interleukin 1 induces leukocyte infiltration and cartilage proteoglycan degradation in the synovial joint. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8749–8753. doi: 10.1073/pnas.83.22.8749. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seckinger P., Klein-Nulend J., Alander C., Thompson R. C., Dayer J. M., Raisz L. G. Natural and recombinant human IL-1 receptor antagonists block the effects of IL-1 on bone resorption and prostaglandin production. J Immunol. 1990 Dec 15;145(12):4181–4184. [PubMed] [Google Scholar]
- Seckinger P., Lowenthal J. W., Williamson K., Dayer J. M., MacDonald H. R. A urine inhibitor of interleukin 1 activity that blocks ligand binding. J Immunol. 1987 Sep 1;139(5):1546–1549. [PubMed] [Google Scholar]
- Stimpson S. A., Dalldorf F. G., Otterness I. G., Schwab J. H. Exacerbation of arthritis by IL-1 in rat joints previously injured by peptidoglycan-polysaccharide. J Immunol. 1988 May 1;140(9):2964–2969. [PubMed] [Google Scholar]
- Stimpson S. A., Esser R. E., Carter P. B., Sartor R. B., Cromartie W. J., Schwab J. H. Lipopolysaccharide induces recurrence of arthritis in rat joints previously injured by peptidoglycan-polysaccharide. J Exp Med. 1987 Jun 1;165(6):1688–1702. doi: 10.1084/jem.165.6.1688. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ulich T. R., Guo K. Z., Remick D., del Castillo J., Yin S. M. Endotoxin-induced cytokine gene expression in vivo. III. IL-6 mRNA and serum protein expression and the in vivo hematologic effects of IL-6. J Immunol. 1991 Apr 1;146(7):2316–2323. [PubMed] [Google Scholar]
- Ulich T. R., Yin S. M., Guo K. Z., del Castillo J., Eisenberg S. P., Thompson R. C. The intratracheal administration of endotoxin and cytokines. III. The interleukin-1 (IL-1) receptor antagonist inhibits endotoxin- and IL-1-induced acute inflammation. Am J Pathol. 1991 Mar;138(3):521–524. [PMC free article] [PubMed] [Google Scholar]
- Wakabayashi G., Gelfand J. A., Burke J. F., Thompson R. C., Dinarello C. A. A specific receptor antagonist for interleukin 1 prevents Escherichia coli-induced shock in rabbits. FASEB J. 1991 Mar 1;5(3):338–343. doi: 10.1096/fasebj.5.3.1825816. [DOI] [PubMed] [Google Scholar]
- Wood D. D., Ihrie E. J., Dinarello C. A., Cohen P. L. Isolation of an interleukin-1-like factor from human joint effusions. Arthritis Rheum. 1983 Aug;26(8):975–983. doi: 10.1002/art.1780260806. [DOI] [PubMed] [Google Scholar]
- van de Loo A. A., van den Berg W. B. Effects of murine recombinant interleukin 1 on synovial joints in mice: measurement of patellar cartilage metabolism and joint inflammation. Ann Rheum Dis. 1990 Apr;49(4):238–245. doi: 10.1136/ard.49.4.238. [DOI] [PMC free article] [PubMed] [Google Scholar]