TKO mice display increased TNF-α, which can be rescued by a genetic cross with Ripk1(^+/−) mice or the anti-inflammatory drug Enbrel. (A) TNF-α, (B) IL-6, and (C) IL-1β positivity in myeloid progenitor and LSK populations in Bid^+/+, DKO, and TKO mice. (D-E) Intracellular cytokine staining for TNF-α (D) and IL-1β (E) in Bid^+/+, TKO, and TKORipk1(^+/−) mouse bone marrow after 5 hours of LPS stimulation (200 ng/mL) + Golgi Plug. Bid^+/+, n = 5; TKO, n = 7; and TKORipk1(^+/−), n = 5. (F) Myeloid progenitor populations and corresponding fold change for Bid^+/+ and TKO mice before and after treatment with Enbrel (TNF decoy receptor). (G) Number of BrdU-positive myeloid progenitors and fold change as in panel F. (H-I) RBCs (10⁶/µL; H, left) and platelet counts (10³/µL; I, right) in Bid^+/+ and TKO mice with and without Enbrel and corresponding fold change. (J) Model diagram for cell death pathways in Bid^+/+, DKO, and TKO mice. In a TKO mouse, the absence of Bax and Bak inhibits the feed-forward caspase amplification, while further loss of Bid results in necrotic cell death. Bid^+/+, n = 4; and TKO, n = 4. *P < .05, ***P < .001, and ****P < .0001. Data represent mean ± SEM. MOMP, mitochondrial outer membrane permeabilization; ns, not significant.