Effects of K-11706 or K-13144 on hemoglobin and erythropoietin. (A) Effects of K-11706 or K-13144 on the inhibiton of hemoglobin concentrations induced by IL-1β or TNF-α in ICR mice. ICR mice were treated with 150 μL PEG by oral administration on days 0 to 5 as a control. Mice were intraperitoneally injected with 1.67 × 10⁴ U (0.33 μg) rmIL-1β on days 0 to 3, 3.33 × 10⁵ U (0.83 μg) rmTNF-α on days 0 to 3, and 3 mg/kg K-11706 or K-13144 by oral tube feeding on days 0 to 5 (n = 5-12). In order to study the effects of K-11706 or K-13144, IL-1β and TNF-α on Epo production in vivo, we removed 0.3 mL blood from the orbital vein at 0, 12, 24, and 36 hours to mimic anemia. ^* indicates significance compared with control, P < .005; ^**, significance compared with IL-1β, P < .05; ^***, significance compared with TNF-α, P < .01. (B) Effects of K-11706 or K-13144 on the inhibition of serum concentrations of Epo induced by IL-1β or TNF-α in ICR mice. Experimental conditions were the same as those described in the legend to panel A (n = 5-9). ^* indicates significance compared with control, P < .05; ^**, significance compared with TNF-α, P < .01.