Collagen-Induced Arthritis in DBA/1 Mice: Cytokine Gene Activation Following Immunization with Type II Collagen

Immunization of DBA/1 mice with bovine type II collagen (CII) in complete Freundʹs adjuvant (CFA) leads to collagen-induced arthritis as evidenced by joint inflammation. In this study, reverse transcription–polymerase chain reaction (RT–PCR) was used to demonstrate the activation of genes encoding for IL-2, IFN-γ, and IL-10 in the lymph nodes from both CII-immunized and control CFA-immunized DBA/1 mice, at Days 10, 40, and 70 after immunization, in the absence of any IL-5 or IL-13 transcription. By quantitative RT–PCR, the levels of IFN-γ mRNA in response to CII could not be quantitatively differentiated from the IFN-γ transcribed in response to CFA alone. In the joints of CII-immunized mice, IL-1β and IL-10 mRNA were found in the absence of IL-5 or IFN-γ. Synovial IL-1β and IL-10 were expressed most strongly at the time of clinical symptoms, 40 days after immunization. Together, these findings suggest that immunization with CII in CFA induces a type 1 response against the adjuvant, giving a cytokine environment which influences the T cells responding to CII to become type 1 T cells. This is manifested here by the appearance of gene activation in synovial tissue of collagen-immunized mice, but not in adjuvant-immunized control animals.