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We have examined the ability of peptidoglycan (PepG) and lipoteichoic acid (LTA) isolated from Staphylococcus aureus to induce the release of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and IL-10 in whole human blood and identified the cellular origins of these cytokines. Both PepG and LTA induced transient increases in TNF-alpha and IL-10 in plasma, with peak values at 6 and 12 h, respectively. IL-6 values increased throughout the experimental period (24 h). The TNF-alpha, IL-6, and IL-10 release induced by PepG and LTA was dose dependent. Only PepG was a potent inducer of TNF-alpha secretion. After stimulation of whole blood with PepG or LTA, very pure populations of monocytes (CD14 positive), T cells (CD2 positive), B cells (CD19 positive), and granulocytes (CD15 positive) were isolated by immunomagnetic separation and analyzed by reverse transcription-PCR for mRNA transcripts encoding TNF-alpha, IL-6, and IL-10. The TNF-alpha mRNA results were inconclusive. In contrast, PepG induced IL-6 and IL-10 mRNA accumulation in both T cells and monocytes. LTA, as well as lipopolysaccharide, induced IL-6 and IL-10 mRNA production in monocytes and possibly in T cells. Whether granulocytes and B cells produce cytokines in response to bacterial stimuli remains obscure. Blockade of the CD14 receptors with monoclonal antibodies (18D11) had no influence on the PepG-induced release of TNF-alpha but attenuated the LTA-induced release of the same cytokine. In conclusion, our data indicate that circulating T cells and monocytes contribute to cytokine production in sepsis caused by gram-positive bacteria.

Fibronectin binds to Streptococcus pyogenes, and this binding is inhibited by lipoteichoic acid (LTA). Previous studies have shown that LTA can be released from S. pyogenes by treatment with penicillin. Penicillin released LTA from both S. pyogenes and Staphylococcus aureus; however, the binding of fibronectin correlated with the amount of LTA released only in the case of S. pyogenes. Contrarily, clindamycin decreased the ability of S. aureus to bind fibronectin without affecting the binding of fibronectin to S. pyogenes. Further studies indicated that LTA does not inhibit the binding of fibronectin to S. aureus. Fibronectin bound to S. pyogenes could be released from the cell surface by penicillin. Immunological analysis of the released fibronectin indicated that LTA was the only surface component which could be detected as a soluble complex with the released fibronectin. These studies suggest that LTA plays a central role in the binding of fibronectin to S. pyogenes and is not involved in the binding of fibronectin to S. aureus.