IMPAIRMENT OF NEUTROPHIL CHEMOTACTIC AND BACTERICIDAL FUNCTION IN CHILDREN INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND PARTIAL REVERSAL AFTER INVITRO EXPOSURE TO GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

Because polymorphonuclear neutrophils are the most important component of host defense against bacteria, we assessed their function in 13 children with asymptomatic and 12 with symptomatic infection with human immunodeficiency virus type 1 (HIV-1), and compared their values with healthy adult control values. The functions assessed were (1) chemotaxis, (2) bacterial phagocytosis, (3) superoxide generation, and (4) bactericidal activity. Chemotaxis of polymorphonuclear neutrophils toward the chemoattractant N-formylmethionyl leucyl phenylalanine (FMLP) was significantly decreased in symptom-free infected children compared with control subjects (p<0.0001), but was increased in children with symptomatic infection (p<0.025). Bactericidal activity of the neutrophils against Staphylococcus aureus was defective in 8 of 12 children with asymptomatic infection (p=0.016), and in 8 of 9 children with symptomatic infection (p<0.00001). Superoxide generation by polymorphonuclear neutrophils on stimulation with FMLP and phagocytosis of S. aureus were normal. Serum from patients with symptomatic HIV-1 infection was not as efficient in low concentrations as normal serum in the ability to opsonize S. aureus. The in vitro bactericidal defect was partially corrected by granulocyte-macrophage colony-stimulating factor (GM-CSF). The results suggest that both cellular (neutrophilis) and humoral defects contribute to the increased incidence of bacterial infections in HIV-1-infected children, and that GM-CSF may improve the defective bactericidal activity of polymorphonuclear neutrophils in these patients. © 1997 Elsevier Science Ltd. All rights reserved.