Figure 2.

Anti-CII antibodies injected either as a cocktail or as individual antibodies induce mechanical hypersensitivity and reduce locomotion before inflammation. (A–C) Anti-CII mAbs (n = 10) induced mechanical hypersensitivity as early as 2 d after injection (A) compared with saline controls (n = 9) in B10.RIII mice. Arthritis scores (B) and incidence (C) were not detectable until day 4 and remained very low also on day 5. (D) Total movement (left) and rearing (right) significantly decreased in B10.RIII mice injected with the anti-CII mAb cocktail (n = 15), compared with controls (n = 19). (E–G) When injected individually, the four mAbs (M2139, UL1, CIIC1, and CIIC2) induced mechanical hypersensitivity similarly to the cocktail (E; n = 5–9/group, B10.RIII mice). No considerable signs of inflammation (F and G) were detected. (H) Total movement (left) and rearing (right) were reduced in M2139 mAb–injected B10.RIII mice (n = 5), compared with saline (n = 5) or isotype control (n = 5). (I–K) Injection of M2139 mAb–induced mechanical hypersensitivity for 21 d (I) even at doses that did not induce visual signs of inflammation (J and K; n = 5, B10.RIII mice). Axes in Fig. 2 (A and E) are interrupted to make the difference between groups clearer to visualize. Data are presented as mean ± SEM. *, P < 0.05; **, P < 0.01; ***, P < 0.001 compared with saline controls. For Fig. 2 E, significance is shown with symbols: * for M2139 and CIIC2 mAbs, # for CIIC1, and † for UL1 compared with saline controls. For Fig. 2 I, significance is shown with symbols: * for 4 mg M2139, # for 2 mg M2139, † for 1 mg M2139, and ‡ for 0.5 mg M2139 compared with each respective baseline.