Endogenous granulocyte colony-stimulating factor production by peripheral blood mononuclear cells in persons with acquired immunodeficiency syndrome

Abstract

Granulocyte colony-stimulating factor (G-CSF) is essential for the regulation of granulopoiesis. A deficiency of endogenously produced G-CSF may account for the relative neutropenia, impaired neutrophil function, and other neutrophil-related responses to infection observed in patients with acquired immunodeficiency syndrome (AIDS). In the present study, heparin-anticoagulated whole blood was obtained from 10 patients with advanced human immunodeficiency virus (HIV) and a diagnosis of AIDS and 9 healthy volunteers. Peripheral blood mononuclear cells (PBMCs) were isolated by density-gradient centrifugation, stimulated with lipopolysaccharide at various concentrations, and kept in culture. G-CSF concentrations in culture supernatants were assayed by enzyme-linked immunosorbent assay after 24 hours. The PBMCs from patients with HIV showed decreased G-CSF production at baseline and at all concentrations of endotoxin, reaching significance at 10,000 ng/mL. The mean peak G-CSF level attained by PBMCs from patients with AIDS at 1000 ng/mL endotoxin was less than the level attained by PBMCs obtained from volunteers at an endotoxin concentration of 50 ng/mL. This decreased G-CSF production in response to endotoxin may explain attenuated neutrophil responses to acute bacterial infections.