Bacterium-dependent induction of cytokines in mononuclear cells and their pathologic consequences in vivo

Viridans streptococci are a heterogeneous group of gram-positive bacteria t hat are normal inhabitants of the mouth. These organisms are thought to con tribute significantly to the etiology of infective endocarditis, although r ecently they have been implicated in serious infections in other settings. Another group of oral bacteria, gram-negative anaerobes, is associated with chronic dental infections, such as periodontal diseases or endodontic lesi on formation, We evaluated the ability of the oral pathogens Streptococcus mutans and Porphyromonas endodontalis to induce a pathogenic response in vi vo, with the goal of quantifying the inflammatory response in soft tissue b y measuring leukocyte recruitment and hard tissues by measuring osteoclasto genesis, S. mutans induced a strong inflammatory response and was a potent inducer of osteoclast formation, while P. endodontalis was not. To further study the mechanisms by which P, endodontalis and S. mutans elicit signific antly different levels of inflammatory responses in vivo, we tested the cap acity of each to induce production of cytokines by mononuclear cells in vit ro. S. mutans stimulated high levels of interleukin-12 (IL-12), gamma inter feron (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha), all of whic h are associated with inflammation, enhanced monocyte function, and generat ion of a Th1 response. In contrast, P. endodontalis stimulated production o f IL-10 but not of TNF-ol, IL-12, or IFN-gamma, These results demonstrate t hat oral pathogens differ dramatically in their abilities to induce inflamm atory and immunoregulatory cytokines,;Moreover, there is a high degree of c orrelation between the cytokine profile induced by these bacteria in vitro and their pathogenic capacity in vivo.