Both the α7nAChR agonist AR-R17779 and nicotine improve, while targeted α7nAChR gene disruption exacerbates CIA. CIA was induced in male and female α7nAChR deficient C57BL/6 mice and wild-type littermates. Clinical arthritis scores are shown over time as mean + SE (A). Significance between groups was determined by comparing the area under the curve (AUC) from d 20 to d 26 (B), **p < 0.005 for t test versus saline. Beginning on d 20 after immunization with type II collagen, male DBA/1 mice were treated with nicotine (400 g/kg; n = 8) or saline, or AR-R17779 (1, 2.5, or 5 mg/kg; n = 15 per dose group) or saline for 7 d. Clinical arthritis scores are shown over time as mean + SE (C, D). Significance between groups was determined by comparing the AUC from d 20 to d 26 (not shown). Arthritis scores were significantly lower in mice treated with nicotine or AR-R17779 at 2.5 mg/kg or 5 mg/kg compared with scores in control animals. Incidence of arthritis in mice treated with AR-R17779 (5 mg/kg) or saline are plotted cumulatively over time (E), *p ≤ 0.05 for Kaplan-Meier survival test versus saline. Panels A and B from a figure in (29) (adapted by permission from BMJ Publishing Group Limited. Annals of the Rheumatic Diseases. Role of the cholinergic nervous system in rheumatoid arthritis: aggravation of arthritis in nicotinic acetylcholine receptor α7 subunit gene knockout mice. Marjolein A van Maanen, Susanne P Stoof, Gregory J LaRosa, Margriet J Vervoordeldonk, Paul P Tak. 69:1717-23, © 2010). Panels C-E adapted by permission from a figure in (30) (Stimulation of Nicotinic Acetylcholine Receptors Attenuates Collagen-Induced Arthritis in Mice. Marjolein A van Maanen, Maria C Lebre, Tom van der Poll, Gregory J LaRosa, Daniel Elbaum, Margriet J Vervoordeldonk, Paul P Tak. Arthritis & Rheumatism. Vol. 60, issue 1. Copyright © 2009 by the American College of Rheumatology).