The Anti-Inflammatory Properties of Interleukin 18 Binding Protein in Rheumatoid Arthritis

K.E.  Khalid; T.B.  Gue; H.  Nie; Mohamed  EL Imam; Nasrden  Yosif; Elhadi  Miskeen

doi:10.52981/sjms.v4i2.1000

K.E. Khalid Department of Biochemistry and Nutrition.
T.B. Gue Joint Immunology Laboratory at the Institute of Health Sciences and Shanghai Institute of Immunology,
H. Nie Joint Immunology Laboratory at the Institute of Health Sciences and Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine and Shanghai Institutes of Biological Sciences, Chinese
Mohamed EL Imam Department of Surgery,
Nasrden Yosif Department of Internal Medicine.
Elhadi Miskeen

DOI: https://doi.org/10.52981/sjms.v4i2.1000

Keywords: IL-18BPa,, Inflammation,, Rheumatoid, Arthritis,, Osteoarthritis

Abstract

Objectives: Interleukin-18 binding protein (IL-18BP) is functioning as a natural anti-inflammatory and immunosuppressive molecule by neutralizing the effects of IL-18 during inflammation. This study aimed to identify the role of IL-18BPa in the regulation of immune responses associated with the pathogenesis of RA.

Materials and Methods: 65 RA patients, 22 OA patients, and 40 sex and age matched healthy donors were enrolled in this study. Synovial specimens were obtained through synovectomy or arthroscopic procedures. SFMC and PBMC were prepared by using Ficoll-Hypaque separation

procedure. Superarray analysis was used to measure the expression profile of immune-related genes in normal PBMC treated with recombinant human IL-18BPa.The mRNA levels of Th1 and Th2 cytokines were measured by Real-time PCR, and the protein levels of IFN-ã, IL-4 were detected by ELISA.

Results: SuperArray analysis of immune related gene expression profile in normal PBMC treated with IL-18BPa indicated decreases in the gene expression of IFN-ã and its regulatory molecules STAT-1 and STAT-2. This study pointed out that IL-18BPa has additional anti-inflammatory property through downregulating the expression of IFN-ã and IL-12, at the same time, upregulating the expression of IL-4 and IL-10. Both IFN-ã and IL-12 could upregulated the mRNA and protein levels of IL-18BPa in both the normal and RA subjects.

Conclusion: Our results demonstrated the importance of IL-18BPa as an immune regulatory molecule and as a promising therapy for treating RA.

References

1. Buckley CD. Treatment of rheumatoid arthritis.Science, medicine and future. BMJ 1997; 315: 236-8.
2. Banda, N. K.A. Vondracek, D. Kraus et al.Mechanisms of inhibition of collagen-in- ducedarthritis by murine IL-18 binding protein. J Immunol2003; 170: 2100.
3. Corbaz, A.T. ten Hove, S. Herren et al. IL-18-binding protein expression by endothelial cells andmacrophages is up-regulated during active Crohn’sdisease. J Immunol 2002; 168: 3608.
4. Choy, E.H., and Panayi, G.S. Cytokine pathwaysand joint inflammation in rheumatoid arthritis. N EnglJ Med 2001; 344: 907-916.
5. Novick, D.S. H. Kim, G. Fantuzzi et al. Rubinstein.Interleukin-18 binding protein: novel modulator of theTh1 cytokine response. Immunity 1999; 10:127.6. Szekanecz, Z., Kim, J., and Koch, A.E. Chemokinesand chemokine receptors in rheuma toid arthritis.Semin Immunol 2003; 15: 15
.7. Arnet, F.C., Edworthy, S.M., Block, D.A et al.(1988). The American Rheumatism Association 1987revised criteria for the classification of rheumatoidarthritis. Arthritis Rheum; 31: 315-24.
8. Bresnihan B, Roux-Lombard P, Murphy E et al.Serum interleukin 18 and interleukin 18 bindingprotein in rheumatoid arthritis. Ann Rheum Dis 2002;61(8): 726-
9. Afkarian M, Sedy JR, Yang J et al. T-bet is aSTAT1-induced regulator of IL-12R expression innaive CD4+ T cells. Nat Immunol 2002; 3(6): 549-57.
10. Lawless VA, Zhang S, Ozes ON et al. STAT-4regulates multiple components of IFN-gammainducingsignaling pathways. J Immunol 2000;165(12): 6803-8.
11. Plater-Zyberk C, Joosten LA, Helsen MM et al.Therapeutic effect of neutralizing endogenous IL-18activity in the collagen-induced model of arthritis. JClin Invest 2001; 108 (12): 1825-32.
12. Lonnemann G, Novick D, Rubinstein M et al.Interleukin-18, interleukin-18 binding protein andimpaired production of interferon-gamma in chronicrenal failure. Clin Nephrol 2003; 60(5): 327-34.
13. Plitz T, Saint-Mezard P, Satho M et al. IL-18binding protein protects against contacthypersensitivity. J Immunol 2003; 171(3): 1164-71.
14. Wyburn K, Wu H, Chen G et al. Interleukin-18affects local cytokine expression but does not impacton the development of kidney allograft rejection. Am JTransplant 2006; 6(11): 2612-21.
15. Kawashima M and Miossec P. Decreased responseto IL-12 and IL-18 of peripheral blood cells inrheumatoid arthritis. Arthritis Res Ther 2004; 6: 39-45.
16. Veenstra KG, Jonak ZL, Trulli S et al. IL-12induces monocyte IL-18 binding protein expression viaIFN-gamma. J Immunol 2002; 168(5): 2282-7.
17. Moller B, Paulukat J, Nold M et al. Interferongammainduces expression of interleukin-18 bindingprotein in fibroblast-like synoviocytes. Rheumatology2003; 42(3): 442-5.
18. Mühl H, Kämpfer H, Bosmann M et al. Interferongammamediates gene expression of IL-18 bindingprotein in nonleukocytic cells. Biochem Biophys ResCommun 2000; 267(3): 960-3.