Two of the well characterized members of this family, IL-1α and IL-1β, have been shown to promote inflammation and fibrosis in SSc, including the heart.[29] Levels of various other IL-1 family cytokines, such as IL-18 and IL-33, have been shown to be increased in both sera and tissue samples from the heart, skin and lung.[30] Raised levels of both IL-1β and IL-33 have been associated with cardiac dysfunction in SSc patients, particularly valvular heart disease and diastolic dysfunction.[29,31] IL-33 binds to suppression of tumorigenicity 2 (ST2) receptor. This evidence concerns the gene IL1A and heart valve disorder.