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  • Title: Proteoglycan (aggrecan)-induced arthritis in BALB/c mice is a Th1-type disease regulated by Th2 cytokines.
    Author: Finnegan A, Mikecz K, Tao P, Glant TT.
    Journal: J Immunol; 1999 Nov 15; 163(10):5383-90. PubMed ID: 10553063.
    Abstract:
    In animal models of arthritis induced with Ags or infectious agents, disease severity correlates with a dominant Th1-type response characterized by a higher ratio of IFN-gamma to IL-4. Analysis of BALB/c mice revealed a genetic predisposition toward developing CD4+ Th2-type responses. The bias toward an IL-4-dominant response in BALB/c mice protects mice from severe Lyme-induced arthritis and spontaneous autoimmune disease. Since BALB/c mice immunized with proteoglycan develop severe arthritis, we were interested in testing whether arthritis is associated with a Th2-type response and thus is different from other arthritic models. BALB/c mice immunized with proteoglycan generated a higher ratio of IFN-gamma to IL-4 that peaks at the onset of arthritis. We investigated whether when Th1 cells were dominant, disease outcome could be modified with pharmacological amounts of Th2 cytokines. Treatment with IL-4 prevented disease and induced a switch from a Th1-type to a Th2-type response. Proinflammatory cytokine mRNA transcripts were reduced in joints of cytokine-treated mice. Th2 cytokine therapy at the time of maximum joint inflammation also suppressed symptoms of disease. Despite the predisposition of BALB/c mice to a Th2-type response, proteoglycan-induced arthritis is a Th1-type disease. The effectiveness of IL-4 treatment was particularly striking because in other models of arthritis, treatment in a similar manner with IL-4 was not sufficient to inhibit arthritis. The effective control of arthritis and the switch from a Th1 to Th2 response suggest that levels of endogenous IL-4 in BALB/c mice may increase their responsiveness to Th2 cytokine therapy.
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