Specificity of the STAT-1 decoy oligodeoxynucleotide (ODN) treatment on the acute and chronic phase of antigen-induced arthritis (AIA). Arthritis was induced in the right knee joint at day 0, 4 h after application of the ODN. (a) Joint swelling after treatment with STAT-1 decoy ODN (STAT-1) and mutant control ODN (STAT mut) (all ODNs 0.25 nmol per knee; n = 8 to 10) in comparison to buffer-treated mice with AIA (control, n = 8 to 10). Joint swelling was assessed as the difference between right (arthritic) and left (untreated) knee joint diameter. (b) Total arthritis score after histological evaluation. Hematoxylin-eosin (HE) stained knee sections were evaluated blindly by grading of inflammation (cell exudate or infiltrate, hyperplasia) and joint destruction (necrosis, erosion and pannus formation). Total arthritis score is defined as the sum of the inflammation and destruction scores. Effects of STAT-1 decoy ODN (STAT-1) in comparison to mutant control ODN (STAT mut) (all ODNs 0.25 nmol per knee joint) on the acute phase (3 days after arthritis induction, d 3; n = 8 to 10) or on the chronic phase of AIA (14 days after arthritis induction, d 14; n = 8 to 10). (c,d) HE-stained sections of arthritic joints 3 days after arthritis induction. Knee joints of STAT-1 decoy ODN-treated mice (d) were less inflamed than joints of buffer-treated control animals (c) (see arrows). F, femur; T, tibia; M, meniscus. (e) Delayed-type hypersensitivity (DTH) reaction on day 7 after arthritis induction. Swelling was expressed as the difference (mm) between the ear thickness before and after antigen injection. The DTH reaction was also diminished in STAT-1 decoy ODN-treated mice, suggesting the involvement of STAT-dependent Tcell activation, whereas the STAT mutant ODN did not display such an effect (f) Effects on the serum levels of IL-6 at day 3 of AIA mice treated with the STAT-1 decoy ODN (STAT-1) or the STAT mutant ODN (STAT mut) (n = 8 to 10). Serum from immunized mice (day 0) served as reference. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001 versus buffer-treated AIA control.