Several cytokines that affect granulocyte functions increase in inflammatory conditions, and it is known that patients on IL-2 therapy have an increased risk of infection. Our objective was to explore the effects of three cytokines, IL-2, IL-2 and TNF, on PMN phagocytosis, with particular reference to the possible effect of IL-w on TNF and IL-1, and the role they may play in the upregulation of Fc R activity in acute bacterial infections, which we had previously reported. Sheep RBC opsonized with IgG were used as targets and phagocytosis by adherent PMN was observed microscopically. Dose response studies showed that phagocytosis was markedly increased by IL-1 and TNF. The combination of IL-1 and TNF, at optimal concentrations, had an additive effect. IL-2 alone did not affect phagocytosis; however, the upregulatory effect noted with TNF, as well as with the combination of TNF and IL-1, was reduced by IL-2. IL-2 did not inhibit II-1 activity. The cytokines did not alter expression of PMN FcR's; there was no increase in binding of 125I-MAbs against FcR I, FcRII or FcRIII. It was shown that IL-2 inhibited the TNF effect by blocking the binding of TNF to PMN. A MAb against the low- affinity IL-2 receptor (anti-Tac), reversed the inhibitory effect of IL-2 on TNF, whereas a MAb against the intermediate-affinity IL-2 receptor (mikbeta1) had no effect. Notably, IL-2 down-regulated TNF only with adherent PMN; it did not affect 125I-TNF binding to PMN nor the TNF upregulation of phagocytosis by PMN that were in suspension. This suggested that a surface-expressed IL-2 receptor on adherent PMN may be involved in IL-2 down-regulation of TNF activity. In agreement with others, we did not detect IL-2 receptors on PMN in suspension by FACS using anti-Tac and mikbeta1; however, both MAb's stained permeabilized PMN by indirect immunofluorescense, and from 500 to 1000 binding sites/adherent PMN were detected using 125I-anti Tac MAb.
