Suppression of cytokine-mediated beta(2)-integrin activation on circulating neutrophils in critically ill patients

Time beta(2) integrin CD11b plays a central role in inflammation and the sy stemic inflammatory response syndrome (SIRS). The CD11b molecule activates in two ways: the density of membrane-bound CD11b up-regulates and the molec ule undergoes a conformational change that confers adhesiveness to counter- receptors. We studied the kinetics of CD11b activation in patients with SIR S. We found a significantly diminished CD11b activation in response to tumo r necrosis factor ex (TNF-alpha). This affected all circulating polymorphon uclear neutrophils (PMN) and was an intrinsic property of the cells and not due to antagonism by soluble TNF-alpha receptors or loss of cellular recep tors for TNF-alpha. Diminished responsiveness correlated with the severity of organ failure and lasted for months in some patients hut had no impact o n mortality. We speculate that reduced CD11b responsiveness in SIRS contrib utes to the high risk of recurrent infection, but that it may also be prote ctive against excessive PMN activation within the vascular space.