Adrenergic β₁- and β₁₊₂-receptor blockade suppress the natural killer cell response to head-up tilt in humans

To evaluate stress-induced changes in blood leukocytes with emphasis on the natural killer (NK) cells, eight male volunteers were followed during three trials of head-up tilt with adrenergic β₁- (metoprolol) and β₁₊₂- (propranolol) blockade and with saline (control) infusions. The β₁- and β₁₊₂-receptor blockade did not affect the appearance of presyncopal symptoms, but the head-up tilt induced a transient lymphocytosis that was abolished by β₁₊₂-receptor blockade but not by β₁-receptor blockade. Head-up tilt also resulted in delayed neutrophilia, which was insensitive to β-receptor blockade. Lymphocyte subset analysis revealed that the head-up tilt resulted in a twofold increase in the percentage and absolute number of CD3^-/CD16⁺ and CD3^-/CD56⁺ NK cells in peripheral blood and that this increase was partially blocked by metoprolol and abolished by propranolol. The NK cell activity on a per NK cell basis did not change during head-up tilt, indicating that the cytotoxic capability of NK cells recruited to circulation is unchanged. The data suggest that the head-up tilt-induced lymphocytosis was due mainly to CD16⁺ and CD56⁺ NK cells and that their recruitment to the blood was inhibited by β₁- and especially β₁₊₂- receptor blockade. Thus stress-induced recruitment of lymphocytes, and of NK cells in particular, is mediated by epinephrine through activation of β- receptors on the lymphocytes.