Macrophage inflammatory protein-1α is induced by human immunodeficiency virus infection of monocyte-derived macrophages

Abstract

Disparate findings have been reported as to whether human immunodeficiency virus (HIV) affects cytokine production by macrophages (MA). We investigated production of different cytokines and of macrophage inflammatory protein (MIP)1α by HIV-1Ba-L- or HIV-1Ada-infected blood-derived MA. Relative to controls, only MIP-1α levels increased twofold to >10-fold in supernatants 2 to 3 weeks postinfection (PI), at the time of maximum virus production; levels of the other chemokines (RANTES, interleukin (IL)-8) and cytokines (IL-1α, IL-3, IL-6, granulocyte-macrophage colony-stimulating factor (GM- CSF), G-CSF, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1) investigated were not affected. MIP-1α mRNA signal assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) was, however, only occasionally greater in cells from infected cultures relative to controls. MIP-1α levels in supernatants remained in the same range as in control cultures when more than 10 mmol/L. Zidovudine was added 24 hours PI, which indicates involvement of virus replication in the effect. Anti-MIP-1α antibody labeling identified a 10% to 25% subset of MA, strongly expressing HLA-DR and CD4, and also stained by anti-IL-6 and anti-TNF-α antibodies. Two weeks PI, dual staining showed that the majority of the 5% to 20% cells that were p24+ belonged to the MIP-1α+ population, which may define a MA subset capable to better sustain HIV replication. MIP-1α induced by HIV replication in MA might play a role in the pathophysiology of HIV infection: in impaired hematopoiesis; or as a CD4+ and CD8+ lymphocyte chemoattractant, by recruiting either or both HIV-susceptible and cytotoxic T lymphocytes to virus replication sites.