SYNTHESIS OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1 RECEPTOR ANTAGONIST, BUT NOT INTERLEUKIN-1, BY HUMAN MONONUCLEAR-CELLS IS ENHANCED BY EXPOSURE OF WHOLE-BLOOD TO SHEAR-STRESS

Extracorporeal circulation exposes blood to shear stress. In many stud ies, researchers reported effects of sheer stress on morphology and fu nction of various blood cells, but effects on cytokine synthesis have not been studied. The authors investigated the effect of sheer stress on the synthesis of interleukin-1 beta, interleukin-1 alpha, tumor nec rosis factor alpha, and interleukin-1 receptor antagonist by human per ipheral blood mononuclear cells. Whole heparinized blood at room tempe rature was exposed to shear stresses of 50, 200, or 500 dyne/cm(2) for 5 min or 30 sec, and to 980 dyne/cm(2) for 5 sec. peripheral blood mo nonuclear cells were then separated from sheared blood and cultured fo r 24 hrs with or without lipopolysaccharide or Staphylococcus epidermi dis. Total (intra + extracellular) cytokine synthesis was measured by specific radioimmunoassay. Viability of cultured peripheral blood mono nuclear cells, determined by trypan blue exclusion and lactate dehydro genase release, was not significantly affected by shear stress. Shear stress without lipopolysaccharide or S. epidermidis stimulation did no t affect synthesis of interleukin-1 or tumor necrosis factor alpha but did enhance synthesis of interleukin-1 receptor antagonist. Lipopolys accharide- or S. epidermidis- induced synthesis of interleukin-1 was n ot significantly altered by sheer stress. In contrast, lipopolysacchar ide-induced tumor necrosis factor alpha synthesis increased with incre asing shear stress and was significantly elevated over unsheared contr ols, whereas S. tumor necrosis factor alpha and lipopolysaccharide- or S. epidermidis-induced interleukin-1 receptor antagonist synthesis we re not significantly enhanced by shear. Therefore, sublytic trauma, su ch as exposure to sheer stress, affects in vitro responses of peripher al blood mononuclear cells to secondary stimuli.