Interleukin-2 bolus therapy induces immediate and selective disappearance from peripheral blood of all lymphocyte subpopulations displaying natural killer activity: Role of cell adhesion to endothelium

As early as 10-15 min after the start of a 30 min interleukin-2 (IL-2) infusion, a rapid, virtually complete disappearance of all natural killer (NK) lymphocyte subpopulations (including both CD3^- CD56⁺ and CD3⁺ CD56⁺ cells with either alpha/beta or gamma/delta T-cell receptor) was observed from peripheral blood. In contrast, the number of T lymphocytes (CD3⁺ CD56^-) was unmodified for at least 2 h after IL-2 injection. The IL-2-induced, rapid disappearance from peripheral blood of NK and NK-like lymphocytes may be related to their massive adherence to the activated endothelium. In this regard, IL-2 infusion caused a very rapid rise of tumour necrosis factor-alpha (TNF-α) plasma concentration, whereas other cytokines, such as interferon-gamma (IFN-γ), were induced only at later times. In vitro experiments indicated that IL-2, either alone or better combined with TNF-α, exerts a rapid and selective stimulatory effect on NK adhesion to endothelial cells. On the basis of these findings, we suggest that the activation of NK lymphocytes induced by IL-2, alone or combined with TNF-α, plays a key role in mediating the massive and selective adherence of NK and NK-like cells following IL-2 bolus infusion.