Figure 4

Necrostatin-1 accelerates death and worsens organ damage after TNFα-mediated shock in the absence of caspase inhibition. (A) Mice were left untreated (open circles) or treated intravenously with mouse TNFα alone (black squares) or in addition to Nec-1 (open triangles). Survival is presented as a Kaplan-Meyer plot (n = 8). (B, C) Three h after TNFα-injection (basic experimental setting is identical to Figure 3A), mice were euthanized and kidneys were harvested and prepared for PAS-staining. Representative sections are demonstrated and a kidney damage score was used for quantification. (D) In an independent approach (basic experimental setting is identical to Figure 3A), 2.5 h after TNFα-injection, mice were euthanized and jejunum was harvested and HE stained. Representative sections are presented. The arrowhead points to the typical appearance of edema within the tunica muscularis that was exclusively visible in the TNFα/zVAD/Nec-1 group. Scale bars, 20 µm (B) and 50 µm (D).