Lymphocyte-neutrophil interactions: opposite effects of interleukin-2 and tumour necrosis factor-beta (lymphotoxin) on human neutrophil adherence

Human neutrophil adherence was enhanced by recombinant human tumour necrosis factor-beta (TNF beta) but suppressed by recombinant human interleukin-2 (IL-2). The opposite effects of these two lymphokines were observed over a range of concentrations consistent with their other biological activities, occurred within 15 min of incubation, and were still evident after 60 min. Pretreatment of neutrophils with both IL-2 and TNF beta resulted in adherence values intermediate between the values obtained with the individual lymphokines. IL-2 suppressed the stimulatory effects of both the chemotactic peptide formyl-methionyl-leucyl-phenyl-alanine (FMLP) and the phorbol ester phorbol myristate acetate (PMA). The combination of TNF beta with either FMLP or PMA produced enhancement of neutrophil adherence which exceeded that of either agent alone. These effects of the lymphokines were not due to endotoxin contamination since their effects were sensitive to heating and insensitive to polymyxin B treatment. These experiments provide further evidence for the critical role of these lymphokines in the regulation of acute and chronic inflammatory processes.