Effects of proinflammatory cytokines and bacterial toxins on neutrophil theologic properties

Objective: To examine the changes in neutrophil deformability, aggregation, and adherence in response to stimulation with proinflammatory cytokines and bacterial toxins. Design: Prospective, randomized trial. Setting: Research laboratory. Subjects: Neutrophils isolated from healthy volunteers. Interventions: Neutrophils were exposed to tumor necrosis factor (TNF)-alpha, interleukin (IL) 1 beta, IL-8, their combination, endo toxin (LPS), lipoteichoic acid (LTA), and staphyloccocal entero toxin B (SEB). Neutrophil deformability was measured as percent neutrophils filtered through 5-mu m diameter filters. Aggregation was measured using a platelet aggregometer. Adherence was determined by examining the binding of neutrophils to albumin coated latex beads. Measurements and Main Results: Exposure to TNF-alpha and IL-1 beta led to significant decreases in neutrophil filterability, which was attenuated by cytochalasin D pretreatment LPS and LTA also decreased deformability, suggesting that these toxins directly stimulated neutrophils independent of cytokines. IL-8 and SEE did not significantly affect neutrophil deformability. TNF-alpha and LPS were associated with significant neutrophil aggregation, which was inhibited by pretreatment with anti-CD18 antibodies. Neutrophil aggregation was not affected by IL-1 beta, LTA, or SEE. TNF-alpha, IL-8, and LPS increased neutrophil adherence, which also was attenuated by pretreatment with anti-CD18 antibodies. IL-1 beta, LTA, and SEE did not significantly affect neutrophil adherence. Conclusions: Cytokines and bacterial toxins differ in their effects on neutrophil deformability, aggregation, and adherence. Of the cytokines examined, TNF-alpha appears to have the greatest direct effects on neutrophil rheology. Similarly, endotoxin appears to have greater direct effects on neutrophil rheology than the Gram-positive bacterial toxins, LTA, and staphylococcal enterotoxins.