In-vitro stimulation of TNF-α from human whole blood by cell-free supernatants of Gram-positive bacteria

Gram-positive bacteria are being recognized increasingly as the cause of shock-like syndromes, clinically indistinguishable from those seen in association with Gram-negative endotoxic shock. Much clinical and experimental data link tumour necrosis factor-α (TNF-α) with the pathogenesis of endotoxic shock, and a number of studies of individual Gram-positive species have also implicated TNF-α. We report here the first systematic study of the ability of cell-free supernatants of common Gram-positive bacteria to induce TNF-α from human peripheral blood monocytes in vitro. Almost all the 63 strains were able to induce TNF-α, although the levels were substantially lower than those obtained from supernatants of Gram-negative bacteria, used as controls. Streptococcus pneumoniae, S. pyogenes, viridans streptococci and coagulase-negative staphylococci were consistently more active than group B and D streptococci. TNF-α induction did not correlate with conventional markers of pathogenicity; amongst strains of Staphylococcus aureus, commensal and blood culture isolates did not induce significantly different amounts of TNF. We conclude that cell-free supernatants of most Gram-positive bacteria are capable of inducing TNF-α from human peripheral blood monocytes in vitro, but the significance of this finding remains to be determined.