Viridans streptococcal isolates from patients with septic shock induce tumor necrosis factor-alpha production by murine macrophages.

Viridans streptococci are an important cause of bacteremia and septic shock in neutropenic patients, especially patients receiving chemotherapeutic agents that induce severe mucositis. The mechanisms by which viridans streptococci cause septic shock are unclear. We hypothesized that septic shock due to viridans streptococci is attributable to host cytokine production. Three clinical isolates of viridans streptococci were evaluated for their ability to induce production of tumor necrosis factor-alpha (TNF-alpha) by RAW 264.7 murine macrophages. These three strains of viridans streptococci induced TNF-alpha in a dose-dependent fashion, and the kinetics of TNF-alpha induction were similar to those observed with a clinical isolate of Escherichia coli.

Lipoteichoic acid from viridans streptococci induces the production of tumor necrosis factor and nitric oxide by murine macrophages.

Bacterial endotoxin or lipopolysaccharide is the major proinflammatory component of gram-negative bacteria, but the components of gram-positive bacteria that trigger the inflammatory cascade are poorly understood. Lipoteichoic acid (LTA) purified from 2 strains of viridans streptococci induced the accumulation of tumor necrosis factor (TNF) mRNA and protein by the murine macrophage cell line RAW 264.7 in a dose- and time-dependent manner. Furthermore, in the presence of recombinant interferon-gamma, LTA from both strains of viridans streptococci provoked the accumulation of inducible nitric oxide (NO) synthase mRNA and the production of NO. Together these observations indicate that LTA can trigger macrophage activation and the production of TNF and NO and suggest that LTA may be an important determinant of the host inflammatory response to gram-positive infection.