Combined cytotoxic impairment and excess IL-18 leads to spontaneous hyperinflammation. Mice of the indicated genotypes were bred and assessed for (A) survival and body weight. Prf1^−/−, Prf1^+/−, Prf1^+/−;Il18tg, and Prf1^−/−Il18tg littermates were compared with littermate sex-matched controls. Similar to published data,^3,7  naïve Prf1^−/− and WT mice demonstrate no difference in spleen weight, Hb, serum IFNg, or IL-18 (data not shown). WT and Il18tg mice were littermates, and their weights were compared with age- and sex-matched Prf^+/− controls. (B) hepatosplenomegaly in a 5-week-old Prf1^−/−Il18tg mouse. (C) Spleen weight, Hb, serum IFNg, and IL-18. (D) percentage of splenic T cells in the indicated genotypes. *Adjusted P < .05, **P < .01, ***P < .001, ***P < .0001 by 1-way ANOVA with Tukey post-test. Significance is only shown for comparisons where adjusted P < .05. Error bars represent SEM. Results are a composite of 2 independent experiments (weight, spleen weight, and Hb) and 3 independent experiments (serum cytokine measurements).