IRAK inhibitor 4 is an interleukin-1 receptor associated kinase 4(IRAK4) inhibitor. In Vitro: Lack of IRAK-4 impairs the production of proinflammatory mediators by macrophages and DCs in response to M. bovis and M. tuberculosis. IRAK-4-/- cells stimulated with E. coli LPS display delayed activation kinetics of all signaling proteins analyzed, and exhibit dramatically reduced p65 phosphorylation. IRAK1/4 (20 μM) has an inhibitory effect on LPS mediated IL-6 production. IRAK1/4 inhibitor do not decrease p38 phosphorylation in AMs. Combination of IRAK1/4 and Rip2 inhibitors inhibits TLR2-mediated cytokine production in sarcoidosis PBMCs and AMs. IRAK4 is overexpressed and activated in T-ALL. IRAK4 mRNA level is elevated in T-ALL cells from patients compared with the levels detected in thymic T cells or T cells from peripheral blood. In Vivo: IRAK-4-/- mice exhibit a greatly reduced survival rate following aerosol infection compared with IRAK-4+/+ or IRAK-4+/- mice. IRAK-4-/- mice show increased bacterial burden in all organs at 15, 30, and 60 d postinfection. MCL1, but not BCL-xL, overrides the therapeutic effects of combinatorial IRAK1/4 inhibitor and ABT-737 therapy in vivo.