title: Bulk cytokine production versus frequency of cytokine-producing cells in HIV1 infection before and during HAART.
abstract: Cytokine imbalances play a major role in HIV immunopathogenesis. This study analyzes simultaneously the frequency of cytokine-producing cells at the single cell level by flow cytometry and the disturbances in cytokine secretion assessed by ELISA in a cohort of asymptomatic HIV1 patients in different stages of CD4 depletion and during antiretroviral therapy (HAART). Early in the disease, there is an increased frequency of IFN-gamma(+) lymphocytes and bulk IFN-gamma production, in parallel with a reduced proportion of IL4(+) cells and IL4 secreted. The two IL4 measurements are significantly correlated. No such correlation was found for IFN-gamma, which is consistent with a large variation in the amount of IFN-gamma released per individual cell. Moreover, HAART was associated with a reduction to normal levels in the bulk IFN-gamma secretion concomitant with a persistency of the overexpanded IFN-gamma(+) cell subset in the peripheral blood. This study emphasizes the importance of using a conjoint approach to assess the cytokine network in trials of antiretroviral and/or immune-based therapies to avoid missing significant effects which are possibly relevant in the clinical setting.
authors.affiliation: Cellular Immunology Unit-CEBIP, Faculty of Medicine of Lisbon, Lisbon, 1649-028, Portugal.
authors.forename: A E
authors.initials: AE
authors.lastname: Sousa
authors.forename: A F
authors.initials: AF
authors.lastname: Chaves
authors.forename: M
authors.initials: M
authors.lastname: Doroana
authors.forename: F
authors.initials: F
authors.lastname: Antunes
authors.forename: R M
authors.initials: RM
authors.lastname: Victorino
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology*; D015497:HIV-1; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents; D016207:Cytokines; D015850:Interleukin-6; D016753:Interleukin-10