Impaired interleukin-8-induced degranulation of polymorphonuclear neutrophils from human immunodeficiency virus type 1-infected individuals

Degranulation of peripheral blood polymorphonuclear leukocytes (PMNLs) was monitored in human immunodeficiency virus (HIV) type 1 (HIV-1)-infected ind ividuals with or without pulmonary tuberculosis (HIV/TB and HIV groups, res pectively) by measuring the release of P-glucuronidase induced by interleuk in-8 (IL-8), This was increased in a dose-dependent manner in the control g roups consisting of healthy blood donors and patients with pulmonary tuberc ulosis. In contrast, PMNLs from the HIV and HIV/TB groups responded recipro cally in the same assay; that is, higher IL-8 input concentrations resulted in the release of less enzyme than lower IL-8 input concentrations, The de granulation response of PMNLs from HIV-1-infected individuals was similarly altered for another agonist, N-formyl-methionyl-leucyl-phenylalanine, sugg esting that impairment of the nonoxidative armature of PMNL was a more gene ralized phenomenon, However, impaired IL-8-induced degranulation was found to be associated with the reduced expression of both IL-8 receptors, A and B, on whole-blood PMNLs from HIV-l-infected patients compared with that on whole-blood PMNLs from healthy persons. The density of IL-8RA in particular , was most reduced on the surfaces of PMNLs from those patients with the po orest degranulation in response to IL-8. Inefficient agonist-induced degran ulation may contribute to the increased susceptibility of HIV-l-infected pe rsons to secondary microbial infections, this being further exacerbated in HIV/TB patients who, in addition, display defects in phagocytosis and oxida tive burst.