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Interleukin-1 (IL-1) and lipopolysaccharide (LPS) induces cellular response through IL-1 receptor (IL-1R) and Toll like receptors (TLR). IL-1 receptor-associated kinase (IRAK and IRAK2) mediates the activation of NF-betaB by IL-1/Toll receptors, which is a pivotal transcription factor mediating inflammatory and immune response. A novel member in the IRAK/Pelle family was recently identified and designated IRAK-M. IRAKs associate with IL-1/Toll receptors after IL-1 or LPS stimulation and the dominant negative mutants of IRAKs inhibit IL-1 or LPS induced NF-betaB activation. Members in IRAK/Pelle family play a central role in IL-1R/TLR mediated inflammatory responses to cytokine IL-1 and LPS.