DIFFERENTIAL REGULATION OF PROINFLAMMATORY AND HEMATOPOIETIC CYTOKINES IN HUMAN MACROPHAGES AFTER INFECTION WITH HUMAN-IMMUNODEFICIENCY-VIRUS

Cells of the macrophage lineage (MAC) play an important role in human immunodeficiency virus (HIV) infection. However, the knowledge on the extent of macrophage involvement in the pathogenesis of HIV infection is still incomplete. In this study we examined the secretory repertoir e of HIV-infected MAC with respect to the proinflammatory cytokines tu mor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, IL-8, and the hematopoietic growth factors M-, G- and granulocy te-macrophage colony stimulating factor (GM-CSF). Using a culture syst em on hydrophobic teflon membranes, blood-derived MO from healthy dono rs were infected with a monocytotropic HIV-1 isolate (HIV-1(D117III)). We analyzed the constitutive and lipopolysaccharides-stimulated secre tion of MO/MAC early after infection as well as in long-term cultured, virus-replicating cells. The release of proinflammatory mediators and hematopoietic growth factors were differentially regulated after infe ction with HIV: the secretion of TNF-alpha, IL-1 beta, IL-6, IL-8 was upregulated, whereas a down-regulation of M-, G-, and GM-CSF could be observed. These results may provide some explanation for the immunolog ical dysfunction, the hematopoietic failure and the chronic inflammato ry disease occuring in HIV-infected patients. (C) 1996 by The American Society of Hematology.