PIA was induced in 8–11 week old rats by an intradermal injection of 100 μl pristane (2,6,10,14-tetramethylpentadecane, 95%, Acros Organics, Morris Plains, NJ, USA) at the dorsal side of the tail base if not stated otherwise. Adjuvant, oil-induced and collagen-induced arthritides were induced by intradermal injections of 100 μl IFA (Difco Laboratories, Detroit, MI, USA) containing 0.4 mg of Mycobacterium butyricum (Difco), 300 μl pure IFA, and 0.3 mg pepsin-digested collagen type II (CII) purified from rat chondrosarcoma [24 ], dissolved in 150 μl 0.1 M acetic acid and emulsified in an equal volume of IFA, respectively. Synthetic pristane was obtained from Sigma-Aldrich (P2870; St. Louis, MO, USA). Treated and non-treated rats or rats subjected to different immunization protocols were housed together in cages. The evaluation of clinical arthritis is described in detail in S1 Text . In brief, 1 point was given for each inflamed knuckle or toe and up to 5 points was given for an affected ankle (in total 15 points per paw, 60 points per rat). Scores were not given for deformations if not accompanied by erythema. The day of disease remission is defined here as the first of at least three consecutive scoring days with declining arthritis scores. The 'first relapse' (Table 1 ) is the first of at least three consecutive scoring days with increasing scores following a period of disease remission. The frequency of chronic arthritis is defined as the proportion of rats with a mean score of ≥5 or at least two days with scores >6 following day 60 after immunization.
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