Peptidoglycan and lipoteichoic acid from Staphylococcus aureus induce tumor necrosis factor alpha, interleukin 6 (IL-6), and IL-10 production in bothT cells and monocytes in a human whole blood model

We have examined the ability of peptidoglycan (PepG) and lipoteichoic acid (LTA) isolated from Staphylococcus aureus to induce the release of tumor ne crosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and IL-10 in whole h uman blood and identified the cellular origins of these cytokines. Both Pep G and LTA induced transient increases in TNF-alpha and IL-10 in plasma, wit h 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 ind uced by PepG and LTA was dose dependent. Only PepG was a potent inducer of TNF-or secretion, After stimulation of whole blood with PepG or LTA, very p ure populations of monocytes (CD14 positive), T cells (CD2 positive), B cel ls (CD19 positive), and granulocytes (CD15 positive) were isolated by immun omagnetic separation and analyzed by reverse transcription-PCR for mRNA tra nscripts encoding TNF-alpha, IL-6, and IL-10, The TNF-alpha mRNA results we re 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. Wheth er granulocytes and B cells produce cytokines in response to bacterial stim uli remains obscure. Blockade of the CD14 receptors with monoclonal antibod ies (18D11) had no influence on the PepG induced release of TNF-alpha but a ttenuated 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 grampositive bacteria.