Calpastatin overexpression inhibits IL-1α and Il-1β synthesis in vitro and in vivo. In vitro, macrophages isolated from WT and CalpTG (TG) mice bones have been exposed to sodium urate crystals (MSU), Silica crystals (Si.), Adenosine TriPhosphate (ATP) or Nigericin (Niger.), with or without priming by Lipopolysaccharides (LPS). IL-1α and IL-1β expression at the mRNA level was globally reduced (ANOVA) by calpastatin overexpression (A,B, n = 4/condition). Similarly, IL-1α and IL-1β cytokine production by macrophages was also globally reduced by calpastatin overexpression, especially IL-1α synthesis after exposure to particulate inflammasome activators MSU and Si. (C,D, *p < 0.05, **p < 0.01 (post test), n = 4/condition). In vivo, MSU crystals have been injected to WT and CalpTG (TG) mice intraperitonally. IL-1α and IL-1β cytokines have been measured early (3 hours) in the peritoneal fluid, their synthesis was dramatically reduced in CalpTG mice (E,F, **p < 0.01, n = 5/group).