The importance of the TH1/TH2 balance in arthritis: is a therapeutically induced TH2 shift beneficial?

Journal/Book: Z Rheumatol 1999; 58:361-362. 1999;

Abstract: W. B. van den Berg Phd Dept. of Rheumatology University Hospital Nijmegen Rheumatoid arthritis is considered as an autoimmune process. It is still debated whether T cells are an important driving force in chronic arthritis or that activated synovial macrophages and fibroblasts are largely sustaining the disease progression in a T cell-independent fashion. Anyway the end effect on the articular cartilage is mainly running through mediators released from the effector cells. The cytokines TNFa and IL-1b are produced in considerable amounts in the inflamed synovial tissue and are major players in this process. If the synovial tissue of RA patients is analysed for mediators of T cell subsets it is clear that there is a relative paucity of IL-4 linked to virtual absence of Th2 cells and dominance of Th 1 cells. In contrast mediators such as IL-10 and TGFb are abundantly found but apart from production by Th2 and Th3 cells it is obvious that most of it will be originating from activated macrophages. IL-4 is the main product of Th2 cells. It is an intriguing pleiotropic cytokine. It has a function in maturation of Th2 cells and in the suppression of Th1 cells. On the other hand it also exerts potent suppressive activity on TNFa and IL-1b production by activated synovial macrophages and has a direct protective effect on IL-1 mediated destructive effects on chrondrocytes in the articular cartilage. As such IL-4 can exert a controlling role on the arthritic process at at least three levels: shifting the balance of Th1/Th2 cells in the direction of 'nondestructive' Th2 dominance direct suppression of production of destructive cytokines and prevention of the impact of destructive cytokines on cartilage and bone. ...

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