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

Area of Science:

• Immunology
• Cardiovascular Biology
• Microbiology

Background:

• Pro-inflammatory cytokines are known to promote blood coagulation.
• Viridans group streptococci are a common cause of infective endocarditis.

Purpose of the Study:

• To investigate the role of pro-inflammatory cytokines induced by oral streptococci in the pathogenesis of viridans endocarditis.
• To identify specific cytokines involved in early endothelial activation.

Main Methods:

• Peripheral blood mononuclear cell (PBMC) cultures were stimulated with oral streptococci.
• Supernatant fluids were analyzed for cytokine activity, particularly endothelial tissue factor (TF) induction.
• Neutralizing antibodies and recombinant cytokines were used to confirm the role of interleukin-1beta (IL-1beta).
• Expression of endothelial adhesion molecules (ICAM-1, E-selectin) was assessed.

Main Results:

• Interleukin-1beta (IL-1beta) was identified as a major early inducer of endothelial tissue factor (TF) activity.
• Recombinant IL-1beta mimicked the TF-inducing activity of PBMC supernatants.
• IL-1beta-rich supernatants upregulated endothelial ICAM-1 and E-selectin expression.
• These adhesion molecules may facilitate the trapping of monocytes and dendritic cells at the infection site.

Conclusions:

• Oral streptococci rapidly induce IL-1beta production by PBMCs.
• This rapid IL-1beta induction contributes to early endothelial activation and TF expression.
• The findings suggest a mechanism by which oral streptococci promote bacterial deposition in fibrin clots, initiating endocarditis.