title: Disturbed secretory capacity for macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta in progressive HIV infection.
abstract: The protective role of beta-chemokines in HIV infection and disease remains controversial. Contradictory findings have been reported possibly as the result of different beta-chemokine detection methods. To test this, peripheral blood lymphocytes from treatment-naive HIV patients, patients on highly active antiretroviral therapy (HAART), and uninfected controls were assessed for intracellular beta-chemokine levels in comparison with levels of beta-chemokine secretion in culture supernatants. HIV patients had significantly higher intracellular levels of macrophages inflammatory protein (MIP)-1 alpha and MIP-1 beta than uninfected control subjects. In contrast, MIP-1 alpha and MIP-1 beta supernatant levels were significantly lower in HIV patients than in controls. Interestingly, both intracellular and supernatant levels of RANTES (regulated on activation, normal T cell expressed and secreted) were significantly increased in HIV patients. Prolonged (> 3 years) administration of HAART in HIV patients normalized the intracellular levels of MIP-1 beta and RANTES and restored the decreased supernatant levels of MIP-1 alpha and MIP-1 beta to levels observed among controls. Significant direct correlations observed between the intracellular and the supernatant levels of beta-chemokines in controls were lost in treatment-naive (except MIP-1 beta) and HAART-treated patients (except RANTES after 3 years of HAART). These data indicate that lymphocytes of HIV patients display a disrupted capacity to secrete the beta-chemokines MIP-1 alpha and MIP-1 beta, which may constitute a mechanism of immune dysfunction in progressive HIV infection. Furthermore, we demonstrated that the detection of beta-chemokines in HIV patients by different methods may indeed result in contradictory findings.
authors.affiliation: Department of Microbiology, Institute of Tropical Medicine, 2000 Antwerp, Belgium. wjennes@itg.be
authors.forename: Wim
authors.initials: W
authors.lastname: Jennes
authors.forename: Chris
authors.initials: C
authors.lastname: Vereecken
authors.forename: Katrien
authors.initials: K
authors.lastname: Fransen
authors.forename: Ann
authors.initials: A
authors.lastname: de Roo
authors.forename: Luc
authors.initials: L
authors.lastname: Kestens
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D018450:Disease Progression; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology
chemical_list: D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins