The present invention relates to the field of infection and inflammation and, more specifically, to the field of pathogen-induced nuclear factor kappa B activation. More specifically, a novel splice variant of MyD88, (MyD88.sub.S), which has been identified encoding a protein that inhibits LPS-induced NF-.kappa.B activation. MyD88.sub.S is a target to inhibit the phenomenon of endotoxin-tolerance that occurs in sepsis.