KLK4 and hereditary angioedema: Joseph et al. suggested that interleukin-1 (IL-1), tumor necrosis factor (TNF)-alpha, and estrogen can promote HAE attacks via stimulation of endothelial cells and augmented activation of the prekallikrein-high-molecular-weight kininogen complex (prekallikrein-HMWK) to generate kallikrein and bradykinin [12].