Figure 1.
The temporal relationship between cytokine production and disease in CIA in the DBA/1 mouse. Studies of cytokine production and assays for the presence of mRNA have indicated that the initial response following CII/CFA challenge is dominated by a Th1 response, with IFN-γ being readily detectable in the lymph nodes, and basal levels of endogenous IL-4 and IL-10 being markedly reduced.71 Around the time of clinical disease onset, the IFN-γ response begins to decline, concomitant with an increase in the levels of IL-4 and IL-10.71,79 The production of IL-10 increases to above prechallenge levels and is maintained. The Th1 response in the lymph nodes is matched by the presence of high level IL-12 production by cells in the spleen and peritoneal cavity.80 Analysis of cytokine production in the joints has revealed that IFN-γ is only present for a limited period around the time of disease onset, while IL-2, IL-4 and IL-5 are undetectable.89 In contrast, the prolonged presence of the cytokines, IL-1, IL-10, TNFα, TGFβ and IL-6 are detected in the joints.88,89