Pharmacological inhibition of RORγt suppresses the Th17 pathway and alleviates arthritis in vivo
Fig 8
Cpd 1 ameliorates antigen-induced arthritis (AiA) responses in Lewis rats.
(A) Rats were immunized twice with methylated BSA (mBSA). Three weeks later, the right knees of the animals were challenged with mBSA in 5% glucose, while the left knees were injected with vehicle (5% glucose). Starting just prior to antigen challenge, cpd 1 was administered twice daily via oral gavage at the indicated doses for 7 days and knee swelling was monitored. The mean ± SEM of the swelling ratios between antigen-challenged and vehicle injected knees are shown (n = 5). Results are representative of two experiments with 5 rats per treatment group. (B) Draining lymph node cells were prepared 7 days after mBSA challenge and stimulated ex vivo with mBSA (200 μg/ml). Frequencies of IL-17A secreting antigen-specific cells were quantified by ELISPOT after 6 h. (C) Diluted sublingual whole blood cells originating from cpd 1- or vehicle-treated animals were re-stimulated with mBSA (50 μg/ml) and after 96 hrs, IL17A concentrations were determined by ELISA. Each point represents mean ± SEM from an individual rat (n = 4–5 readings/animal). *, P < 0.05; **, P < 0.01; ***, P < 0.001 Dunnett´s test.