Increased plasma free cyclic-AMP levels following major trauma and their relevance to the immune response

Abstract

Background: Following injury, neutrophil mobilisation is an important element of the immune response. The ideal features of an agent responsible for this mobilisation would include the ability to mobilise neutrophils without activating them, and rapid reversibility. This study investigates the hypothesis that raised levels of plasma adrenaline following trauma act via cyclic adenosine monophosphate (cAMP) to mobilise neutrophils, and measures the amount of cAMP extruded from cells into the plasma following injury. Methods: 20-ml samples of venous blood were drawn from 34 trauma patients within 3 h of injury and divided between three sample tubes: (1) ethylene diamine tetra-acetic acid anticoagulant (EDTA) for full blood count; (2) cooled EDTA for cAMP levels; and (3) cooled lithium heparin for catecholamines. The latter two tubes were immediately centrifuged at low temperature and the supernatant plasma deep frozen pending analysis. Adrenaline was measured using high pressure liquid chromatography (HPLC) and cAMP measured by an enzyme immunoassay technique. Results: 34 patients, six of whom had sustained minor trauma (ISS 1-8), 12 moderate trauma (ISS 9-15) and 16, major trauma (ISS 16 and above) were studied. Median age was 39 years (range 16-77) and 30 patients were male. Plasma adrenaline levels were available for 28 of the patients. Plasma free cAMP levels were significantly raised in patients with major trauma (P < 0.006). There were positive correlations between the plasma levels of cAMP and adrenaline (rho 0.660, P = 0.011), adrenaline and neutrophil count (rho 0.654, P = 0.01) and cAMP and neutrophil count (rho 0.508, P = 0.013). Conclusions: Evidence is presented of the possible inter-relationships between neutrophil counts, adrenaline levels and cAMP levels following injury, supporting the proposition that neutrophil mobilisation pathways are activated early via β-adrenergic stimulation. (C) 2000 Elsevier Science Ireland Ltd.