Arthritis was induced in 125- to 140-g female Lewis rats (Harlan) by a single intraperitoneal injection of peptidoglycan–polysaccharide complexes from group A SCW purchased from Lee Laboratories (Grayson, GA). The disease course was biphasic with an acute inflammatory non-T cell-dependent phase on days 1 to 3 followed by a chronic T cell-ependent inflammatory-erosive arthritis developing over days 14 to 28. Animals developing the acute inflammatory phase were pooled into groups of seven to eight animals per group and dosed with PF-3644022 or methylcellulose-Tween 20 vehicle by oral gavage (1 ml) twice a day for days 10 to 21. Hind paw swelling volumes were measured on day 21 with a displacement plethysmometer

PF-3644022 was added to human whole blood (HWB) ex vivo 1 h before stimulation with 100 ng/ml LPS at 37°C. TNFalpha was measured 4 h poststimulation by assaying plasma with a human TNFalpha MSD kit. TNFalpha, IL-1, IL-6, and IL-8 in plasma was also measured after 16-h LPS stimulation of HWB by using a four-plex human cytokine MSD plate