The role of norepinephrine and alpha-adrenergic receptors in acute stress-induced changes in granulocytes and monocytes

Abstract

Objective Acute stress induces redistribution of circulating leucocytes in humans. Whereas effects on lymphocytes as adaptive immune cells are well-understood, the mechanisms underlying stress effects on granulocytes and monocytes as innate immune blood cells are still elusive. We investigated whether the stress hormone norepinephrine (NE) and α-adrenergic receptors (α-ADRs) may play a mediating role.Methods In a stress study, we cross-sectionally tested in 44 healthy men for associations between stress-induced NE increases and simultaneous granulocyte and monocyte cell count increases, as measured immediately before and several times after the Trier Social Stress Test. In a subsequent infusion study, 21 healthy men participated in three different experimental trials with sequential infusions of 1 and 15-min duration with varying substances [saline as placebo, the non-specific α-ADR blocker phentolamine (2.5mg/min), and NE (5μg/min)]: trial1=saline+saline, trial2=saline+NE, trial3=phentolamine+NE. Granulocyte and monocyte cell numbers were assessed before, immediately after, 10min, and 30min after infusion procedures.Results In the stress study, higher NE related to higher neutrophil stress changes (β=.31,p=.045, R2change=.09), but not epinephrine stress changes. In the infusion study, saline+NE induced significant increases in neutrophil (F(3/60)=43.50,p<.001,η2=.69) and monocyte (F(3/60)=18.56,p<.001,η sup>2=.48) numbers compared to saline+saline. With phentolamine+NE, neutrophil (F(3/60)=14.41,p<.001,η2=.42) and monocyte counts (F(2.23/44.6)=4.32,p=.016,η2=.18) remained increased compared to saline+saline but were lower compared to saline+NE (neutrophils: F(3/60)=19.55,p<.001,η 2=.494, monocytes: F(3/60)=2.54,p=.065,η2=.11) indicating partial mediation by α-ADRs. Trials did not differ in eosinophil and basophil count reactivity.Conclusions Our findings suggest that NE-induced immediate increases in neutrophil and monocyte numbers resemble psychosocial stress effects and can be reduced by blockade of α-ADRs.