IL-21 and IL-2 inhibit angiogenesis in vivo. (A,B) Treatment of CAMs with 200 ng/mL IL-2 reduces vessel formation in CAMs, whereas IL-21 does not affect the number of vessels in CAMs (n = 7 for each group). Morphologic examination shows that vessels in CAMs treated with 20 ng/mL or 200 ng/mL IL-21 are tortuous and irregular compared with control CAMs (B). (C) Images of CD31 staining of EF7 tumor sections of mice treated with PBS (control), 20 μg of IL-21, or 2000 IU of IL-2 (images seen through a Leica DM5000B microscope, Leica Microsystems, Rijswijk, The Netherlands). (D) IL-2 (n = 4) and IL-21 (n = 5) treatment reduced microvessel density in tumor tissues compared with control (PBS, n = 5). Results are relative mean values (**P < .005, *P < .05, compared with control).