IN-VIVO GENE-EXPRESSION OF TYPE-1 AND TYPE-2 CYTOKINES IN SYNOVIAL TISSUES FROM PATIENTS IN EARLY STAGES OF RHEUMATOID, REACTIVE, AND UNDIFFERENTIATED ARTHRITIS

It has been reported that the mRNA of the type 1 cytokine, interferon- gamma (IFN-gamma)-but not the type 2 cytokine interleukin-4 (IL-4)-is detected in synovial tissues of rheumatoid arthritis (RA) patients, wh ereas both IFN-gamma and IL-4 mRNA are detected in reactive arthritis (ReA). To evaluate such data more extensively, we obtained 208 synovia l specimens in a prospective study of 52 early synovitis patients (13 RA, II ReA, 28 undifferentiated oligoarthropathy) and analyzed type 1 and type 2 cytokine mRNA expression in specimens containing sufficient mRNA. Using a nested reverse transcriptase polymerase chain reaction technique, we measured the relative mRNA levels of 10 cytokines and CD 3 delta chain. We detected IL-10, IL-15, and CD3 delta chain mRNA in a ll RA and ReA patients and frequently detected tumor necrosis factor-a lpha, IL-1 beta, and IFN-gamma mRNA. IL-6 and IL-12 p40 mRNA were dete cted in approximately one-half of the patients. We also detected great er amounts of IL-2 and IFN-gamma mRNA in ReA than were detected in RA. However, we rarely detected IL-4 or IL-13 mRNA. Similar cytokine prof iles were observed in undifferentiated oligoarthropathy. The amounts o f cytokine mRNAs, except for IL-10, in specimens from the patients tak ing prednisone or second-line antirheumatic drugs tended to be less th an in specimens from the patients taking neither prednisone nor second -line antirheumatic drugs. These results suggest that cytokine mRNA pr ofiles in patients with RA, ReA, and undifferentiated arthritis in the ir early stages are skewed toward proinflammatory macrophage-derived a nd type 1 cytokines. IL-10-not IL-4 or IL-13-mRNA appears to be the ma jor antiinflammatory cytokine mRNA. Drug therapy is associated with de pressed proinflammatory and type 1 cytokine mRNA production. The diffe rences in the expression of IL-2 and IFN-gamma mRNA between RA and ReA may reflect unique etiological or host factors associated with the ea rly stages of these diseases.