Interleukin-32 alpha overexpression in mice increased the lethality of lipopolysaccharide (LPS)-induced endotoxin shock. Endotoxin shock was induced in both transgenic (Tg) mice (n = 24) and wild-type (Wt) mice (n = 24) by intraperitoneal injection of LPS with D-galactosamine. Twelve mice of each group were simultaneously administered etanercept. All mice were monitored for survival up to 48 hours. Survival rate was significantly worse in the Tg group than in the Wt group (*P < 0.05). Etanercept protected against endotoxin shock in both groups (a). Temporal changes in TNFα levels were measured by real-time polymerase chain reaction for liver and spleen lysate or. enzyme-linked immunosorbent assay for blood serum. Levels of tumor necrosis factor-alpha (TNFα) mRNA and protein peaked at 1 hour after LPS injection in the liver (b), spleen (c), and serum (d) from Tg and Wt mice, but levels were much higher in Tg mice than in Wt mice (*P < 0.05, **P < 0.01). The values are expressed as the mean ± standard deviation for four different mice. GAPDH, glyceraldhyde-3-phosphate dehydrogenase.