title: Immunodysregulation of HIV disease at bone marrow level.
abstract: Hematological abnormalities frequently occur in patients infected with HIV-1. Increasing evidence indicates that bone marrow (BM) suppression results from viral infection of accessory cells, with impaired stromal function and alteration of hematopoietic growth factor network. We investigated the effects of antiretroviral therapy on cytokine and chemokine production by BM cells and stromal cells, in a group of HIV-1-infected subjects before and during treatment. Compared with uninfected controls, an altered cytokine and chemokine production by BM cells has been observed before treatment, characterised by decreased IL-2 and elevated TNF-alpha, MIP-1alpha, MIP-1beta, and RANTES levels, along with a defective BM clonogenic activity. Antiretroviral therapy determined an amelioration of stem cell activity, a restoration of stromal cell pattern and functions, and an increased IL-2 production at BM level and a decrease of Fas expression on progenitor cells, in parallel with the diminution of TNF-alpha levels. HIV-1 protease inhibitors (PIs) may improve hematopoietic functions owing to their direct effects on the BM progenitor cells. Ritonavir and indinavir increased the colony growth of BM obtained either from HIV-1-infected patients or from normal individuals, in parallel with the normalization of functional and morphologic characteristics of stromal cells.
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Clinical Medicine, University of Rome La Sapienza, Viale dell'Università, Rome 37-00185, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Isgrò
authors.forename: Alessandro
authors.initials: A
authors.lastname: Aiuti
authors.forename: Wilma
authors.initials: W
authors.lastname: Leti
authors.forename: Claudia
authors.initials: C
authors.lastname: Gramiccioni
authors.forename: Antonella
authors.initials: A
authors.lastname: Esposito
authors.forename: Ivano
authors.initials: I
authors.lastname: Mezzaroma
authors.forename: Fernando
authors.initials: F
authors.lastname: Aiuti
mesh_terms: D001854:Bone Marrow Cells / Q000473:pathology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans
chemical_list: D017320:HIV Protease Inhibitors