TLR2, TLR4, CD14, CD11b and CD11c expression on monocyte surfaces and cytokine production in septic patients

Bacterial recognition and induced cellular activation is fundamental for the host control of infection, yet the limit between protective and harmful response is still inexact. Forty-one patients were enrolled in this study: 14 with sepsis, 12 with severe sepsis, and 15 with septic shock. Seventeen healthy volunteers (HV) were included as controls. The expression of TLR2, TLR4, CD14, CD11b and CD11c was analyzed on monocyte surfaces in whole blood. sCD14 was measured in serum and TNF-α, IL-6 and IL-10 cytokine levels were measured in PARTICLE supernatants following LPS, IL-1β and TNF-α stimuli by ELISA. An increase in sCD14 and a decreased mCD14 were found in patients as compared with HV (P < 0.001). However, no differences in the expression of TLR2, TLR4 and CD11c were found among the groups. A trend towards differential expression of CD11b was observed, with higher values found in patients with sepsis as compared with HV. A negative regulation of the inflammatory cytokine production was observed in severe sepsis and shock septic patients in relation to the sepsis and HV, regardless of the stimulus. No significant difference in IL-10 production was found among the groups. In this study we show that the inflammatory response is associated with the continuum of clinical manifestations of sepsis, with a strong inflammatory response in the early phase (sepsis) and a refractory picture in the late phases (severe sepsis and septic shock). Correlation between cell surface receptors and cytokine production after IL-1β and TNF-α stimuli and the observation of a single and same standard response with the different stimulus suggest a pattern of immunology response that is not dependent only on the expression of the evaluated receptors and that is likely to have a regulation in the intracellular signaling pathways.