Blocking of Interleukin-17 During Reactivation of Experimental Arthritis Prevents Joint Inflammation and Bone Erosion by Decreasing RANKL and Interleukin-1

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 2005 Jun 24

PMID 15972960

Citations 114

Authors

Marije I Koenders

Erik Lubberts

Birgitte Oppers-Walgreen

Liduine van den Bersselaar

Monique M Helsen

Franco E Di Padova

Annemieke M H Boots

Hermann Gram

Leo A B Joosten

Wim B van den Berg

Affiliations

Soon will be listed here.

Abstract

Rheumatoid arthritis is characterized by an intermittent course of disease with alternate periods of remission and relapse. T cells, and in particular the T-cell cytokine interleukin-17 (IL-17), are expected to be involved in arthritic flares. Here, we report that neutralizing endogenous IL-17 during reactivation of antigen-induced arthritis prevents joint inflammation and bone erosion. Synovial IL-17 mRNA expression was clearly up-regulated during primary arthritis and was further enhanced after antigen rechallenge. Neutralization of IL-17 significantly prevented joint swelling at day 1 of flare and significantly suppressed joint inflammation and cartilage proteoglycan depletion at day 4, as assessed by histology. Blocking IL-17 also clearly reduced bone erosions. Cathepsin K, a marker of osteoclast-like activity, and synovial RANKL mRNA expression were both suppressed. The degree of bone erosions strongly correlated with the severity of joint inflammation, suggesting that anti-IL-17 treatment reduced bone erosion by suppressing joint inflammation. Interestingly, blocking IL-17 suppressed synovial expression of both IL-1beta and tumor necrosis factor-alpha, whereas blocking IL-1 did not affect tumor necrosis factor-alpha levels. These data indicate that IL-17 is an important upstream mediator in joint pathology during flare-up of experimental arthritis.

Citing Articles

Neutrophil extracellular traps as immunofibrotic mediators in RA-ILD; pilot evaluation of the nintedanib therapy.

Venetsanopoulou A, Ntinopoulou M, Papagianni E, Koletsos N, Voulgari P, Chrysanthopoulou A Front Immunol. 2024; 15:1480594.

PMID: 39507540 PMC: 11538023. DOI: 10.3389/fimmu.2024.1480594.

Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases.

Zeng J, Li M, Zhao Q, Chen M, Zhao L, Wei S J Pharm Anal. 2023; 13(6):545-562.

PMID: 37440911 PMC: 10334362. DOI: 10.1016/j.jpha.2023.05.009.

Salidroside affects the Th17/Treg cell balance in aplastic anemia via the STAT3/HIF-1α/RORγt pathway.

Liu Z, Chen L, Xiong D, Zhan Y, Liu J, Ouyang L Redox Rep. 2023; 28(1):2225868.

PMID: 37439434 PMC: 10348039. DOI: 10.1080/13510002.2023.2225868.

Synoviocytes and skin fibroblasts show opposite effects on IL-23 production and IL-23 receptor expression during cell interactions with immune cells.

Noack M, Miossec P Arthritis Res Ther. 2022; 24(1):220.

PMID: 36088336 PMC: 9463863. DOI: 10.1186/s13075-022-02904-9.

Analysis of combined deficiency of interleukin-1 and -6 versus single deficiencies in TNF-mediated arthritis and systemic bone loss.

Hayer S, Niederreiter B, Kalkgruber M, Wanic K, Maissner J, Smolen J Bone Joint Res. 2022; 11(7):484-493.

PMID: 35801532 PMC: 9350695. DOI: 10.1302/2046-3758.117.BJR-2021-0481.R1.

References

Starnes T, Robertson M, Sledge G, Kelich S, Nakshatri H, Broxmeyer H . Cutting edge: IL-17F, a novel cytokine selectively expressed in activated T cells and monocytes, regulates angiogenesis and endothelial cell cytokine production. J Immunol. 2001; 167(8):4137-40. DOI: 10.4049/jimmunol.167.8.4137. View

Brackertz D, Mitchell G, Vadas M, Mackay I . Studies on antigen-induced arthritis in mice. III. Cell and serum transfer experiments. J Immunol. 1977; 118(5):1645-8. View

Cai L, Yin J, Starovasnik M, Hogue D, Hillan K, Mort J . Pathways by which interleukin 17 induces articular cartilage breakdown in vitro and in vivo. Cytokine. 2001; 16(1):10-21. DOI: 10.1006/cyto.2001.0939. View

Bush K, Farmer K, Walker J, Kirkham B . Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin-17 receptor IgG1 Fc fusion protein. Arthritis Rheum. 2002; 46(3):802-5. DOI: 10.1002/art.10173. View

Starnes T, Broxmeyer H, Robertson M, Hromas R . Cutting edge: IL-17D, a novel member of the IL-17 family, stimulates cytokine production and inhibits hemopoiesis. J Immunol. 2002; 169(2):642-6. DOI: 10.4049/jimmunol.169.2.642. View

Lens J, van den Berg W, van de Putte L, Berden J, Lems S . Flare-up of antigen-induced arthritis in mice after challenge with intravenous antigen: effects of pre-treatment with cobra venom factor and anti-lymphocyte serum. Clin Exp Immunol. 1984; 57(3):520-8. PMC: 1536280. View

van den Broek M, van den Berg W, van de Putte L . Monoclonal anti-Ia antibodies suppress the flare up reaction of antigen induced arthritis in mice. Clin Exp Immunol. 1986; 66(2):320-30. PMC: 1542525. View

Chomczynski P, Sacchi N . Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987; 162(1):156-9. DOI: 10.1006/abio.1987.9999. View

van den Broek M, van Bruggen M, Stimpson S, Severijnen A, van de Putte L, van den Berg W . Flare-up reaction of streptococcal cell wall induced arthritis in Lewis and F344 rats: the role of T lymphocytes. Clin Exp Immunol. 1990; 79(2):297-306. PMC: 1534749. DOI: 10.1111/j.1365-2249.1990.tb05194.x. View

10.

Jacobs M, van den Hoek A, van Lent P, van De Loo F, van de Putte L, van den Berg W . Role of IL-2 and IL-4 in exacerbations of murine antigen-induced arthritis. Immunology. 1994; 83(3):390-6. PMC: 1415042. View

11.

van De Loo F, Joosten L, van Lent P, Arntz O, van den Berg W . Role of interleukin-1, tumor necrosis factor alpha, and interleukin-6 in cartilage proteoglycan metabolism and destruction. Effect of in situ blocking in murine antigen- and zymosan-induced arthritis. Arthritis Rheum. 1995; 38(2):164-72. DOI: 10.1002/art.1780380204. View

12.

van de Loo A, Arntz O, Bakker A, van Lent P, Jacobs M, van den Berg W . Role of interleukin 1 in antigen-induced exacerbations of murine arthritis. Am J Pathol. 1995; 146(1):239-49. PMC: 1870767. View

13.

Buchner E, Brauer R, Schmidt C, Emmrich F, Kinne R . Induction of flare-up reactions in rat antigen-induced arthritis. J Autoimmun. 1995; 8(1):61-74. View

14.

Idogawa H, Imamura A, Onda M, Umemura T, Ohashi M . Progression of articular destruction and the production of tumour necrosis factor-alpha in antigen-induced arthritis in rabbits. Scand J Immunol. 1998; 46(6):572-80. DOI: 10.1046/j.1365-3083.1997.d01-174.x. View

15.

Jovanovic D, Di Battista J, Martel-Pelletier J, Jolicoeur F, He Y, Zhang M . IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages. J Immunol. 1998; 160(7):3513-21. View

16.

Chabaud M, Fossiez F, Taupin J, Miossec P . Enhancing effect of IL-17 on IL-1-induced IL-6 and leukemia inhibitory factor production by rheumatoid arthritis synoviocytes and its regulation by Th2 cytokines. J Immunol. 1998; 161(1):409-14. View

17.

Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S . IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest. 1999; 103(9):1345-52. PMC: 408356. DOI: 10.1172/JCI5703. View

18.

Chabaud M, Durand J, Buchs N, Fossiez F, Page G, Frappart L . Human interleukin-17: A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum. 1999; 42(5):963-70. DOI: 10.1002/1529-0131(199905)42:5<963::AID-ANR15>3.0.CO;2-E. View

19.

Lubberts E, Joosten L, Oppers B, van den Bersselaar L, Kolls J, Schwarzenberger P . IL-1-independent role of IL-17 in synovial inflammation and joint destruction during collagen-induced arthritis. J Immunol. 2001; 167(2):1004-13. DOI: 10.4049/jimmunol.167.2.1004. View

20.

van den Berg W, Joosten L, van De Loo F . TNF alpha and IL-1 beta are separate targets in chronic arthritis. Clin Exp Rheumatol. 1999; 17(6 Suppl 18):S105-14. View