Can Adrenaline Cause Leukocytosis?
Yes, adrenaline (epinephrine) definitively causes leukocytosis through rapid mobilization of white blood cells from the marginal pool, spleen, bone marrow, and lymphatics, with effects occurring within 5 minutes of administration and typically resolving within 25 minutes. 1
Mechanism and Time Course
Adrenaline-induced leukocytosis occurs through a biphasic response:
Phase 1 (Immediate, <30 minutes): Rapid lymphocyte mobilization, predominantly affecting natural killer (NK) cells, with total blood leucocytes increasing to approximately 220% of baseline within 5 minutes 1, 2
Phase 2 (Later): Granulocyte increases with relative lymphopenia, as neutrophilic granulocytes rise to about 160% of baseline 1, 3
The response is transient, with cell concentrations returning to baseline within 25 minutes after adrenaline injection 1
Specific Cell Populations Affected
The most responsive leukocyte subsets include 4:
- CD16+CD56dim cytotoxic NK cells (most prominent increase)
- CCR7-CD45RA+CD8+ effector T cells
- CD4-CD8- gamma/delta T cells
- CD3+CD56+ NKT-like cells
- CD14dimCD16+ proinflammatory monocytes
Both T and B lymphocytes are mobilized to approximately 230-250% of baseline concentrations 1
Sources of Mobilized Cells
Multiple anatomical compartments contribute substantially to this leukocytosis 1:
- Marginal pool: Primary source for both lymphocytes and granulocytes 2, 5
- Spleen: Significant contributor (splenectomized rats show markedly reduced response) 1
- Bone marrow: Substantial contribution evidenced by increased band-nucleated granulocytes 1
- Lymphatics: Thoracic duct drainage significantly reduces the response 1
- Lung: 20-25% of neutrophils are retained in first pass; exercise and catecholamines accelerate their release 5
Receptor Mechanisms
The leukocytosis involves distinct adrenergic pathways 2:
- Beta-2 adrenoceptors: Mediate lymphocyte mobilization (particularly NK cells)
- Alpha-adrenoceptors: Mediate granulocyte increases
- CD11a/CX3CR1: These adhesion molecules correlate strongly with adrenergic leukocytosis (r = 0.86 and 0.78, p < 0.005) 4
Propranolol (beta-blocker) blocks the polymorphonuclear leucocytosis response 3
Clinical Relevance
Important caveat: This leukocytosis is a normal physiological response and should not be confused with pathological leukocytosis 1, 2. The phenomenon represents mobilization of cytotoxic effector cells that provide immediate protection from invading pathogens as part of the fight/flight response 2, 4
The response is not blood-flow dependent, as organ perfusion remains unaltered after adrenaline injection despite significant cell mobilization 1
Repeated Exposure Effects
Repeated daily administration of exogenous adrenaline increases basal total leucocyte and polymorph counts while decreasing lymphocyte counts, suggesting sensitization of the system responsible for polymorph release from bone marrow 3