Rapid tissue factor induction by oral streptococci and monocyte-IL-1beta

The ability of pro-inflammatory cytokines to promote coagulation prompted the hypothesis that pro-inflammatory cytokines induced by oral streptococci might play a role in the pathogenesis of viridans endocarditis. We used supernatant fluids from peripheral blood mononuclear monocyte (PBMC) cultures, stimulated for just 4-6 hrs with representative streptococcal isolates, to study cytokines that promoted endothelial tissue factor (TF) activity. Neutralizing antibodies demonstrated that interleukin-1beta (IL-1beta) was a major early endothelial TF inducer, and that recombinant IL-1beta was comparable with the supernatant fluid in activity. IL-1beta-rich supernatant fluids from oral streptococci-stimulated or lipopolysaccharide-stimulated PBMC cultures up-regulated the expression of endothelial ICAM-1 and E-selectin. These molecules could help trap TF-producing monocytes or dendritic cells bearing streptococci at the site. Thus, the rapid IL-1beta-inducing capacity of oral streptococci could facilitate the early deposition of bacteria in fibrin clots and promote endocarditis.