This study investigates the role of IL-1β and IL-1α in tumor invasiveness and angiogenesis. The authors found that microenvironmental IL-1β is crucial for in vivo angiogenesis and invasiveness of different tumor cells, while IL-1α plays a less significant role. In IL-1β knockout (KO) mice, local tumor or lung metastases of B16 melanoma cells were not observed compared to wild-type (WT) mice. Angiogenesis was assessed by recruiting blood vessel networks into Matrigel plugs containing B16 melanoma cells, which was present in WT mice but absent in IL-1β KO mice. Exogenous IL-1α partially restored the angiogenic response in IL-1β KO mice. In IL-1α KO mice, local tumor development and angiogenic response were less pronounced than in WT mice but significantly higher than in IL-1β KO mice. These effects were observed in melanoma, DA/3 mammary, and prostate cancer models. IL-1 also contributed to the production of vascular endothelial cell growth factor (VEGF) and tumor necrosis factor (TNFα) in cocultures of peritoneal macrophages and tumor cells. The anti-angiogenic effects of IL-1 receptor antagonist (IL-1Ra) suggest a potential therapeutic role in cancer, in addition to its current use in rheumatoid arthritis.This study investigates the role of IL-1β and IL-1α in tumor invasiveness and angiogenesis. The authors found that microenvironmental IL-1β is crucial for in vivo angiogenesis and invasiveness of different tumor cells, while IL-1α plays a less significant role. In IL-1β knockout (KO) mice, local tumor or lung metastases of B16 melanoma cells were not observed compared to wild-type (WT) mice. Angiogenesis was assessed by recruiting blood vessel networks into Matrigel plugs containing B16 melanoma cells, which was present in WT mice but absent in IL-1β KO mice. Exogenous IL-1α partially restored the angiogenic response in IL-1β KO mice. In IL-1α KO mice, local tumor development and angiogenic response were less pronounced than in WT mice but significantly higher than in IL-1β KO mice. These effects were observed in melanoma, DA/3 mammary, and prostate cancer models. IL-1 also contributed to the production of vascular endothelial cell growth factor (VEGF) and tumor necrosis factor (TNFα) in cocultures of peritoneal macrophages and tumor cells. The anti-angiogenic effects of IL-1 receptor antagonist (IL-1Ra) suggest a potential therapeutic role in cancer, in addition to its current use in rheumatoid arthritis.