title: Intracellular cytokines may model immunoregulation of abacavir hypersensitivity in HIV-infected subjects.
abstract: BACKGROUND
  The clinical treatment of patients with HIV and adverse drug events may be enhanced by an understanding of the underlying mechanisms. About 4% of patients with HIV receiving the potent antiretroviral drug abacavir develop a hypersensitivity reaction. This idiosyncratic reaction appears to have an immunologic component that has yet to be defined. Given that the T-cell type 2 cytokine IL-4 may be overproduced by patients with allergy or other immunologic dysregulation, an index cytokine profile could help elucidate the character of a drug-specific hypersensitivity reaction.
  
  
  OBJECTIVE
  Quantitation of the production of the type 2 IL-4 and the counterregulatory type 1 cytokine IFN-gamma in patients with abacavir-related hypersensitivity.
  
  
  METHODS
  Intracellular cytokines were enumerated in blood T cells by flow cytometry. Subjects were grouped for evaluation as patients with a hypersensitive response after abacavir treatment, patients initiating abacavir who also were evaluated again after 1 month on abacavir, patients on abacavir for 6 months without hypersensitivity, and HIV-naive control individuals.
  
  
  RESULTS
  There was a significant association between increased IL-4 production by CD4 and CD8 T lymphocytes and hypersensitivity reactions to abacavir. Lymphocytes from hypersensitive subjects expressed CD28 and the anti-HIV chemokine macrophage inflammatory protein 1beta with a frequency comparable with HIV-naive control cells, suggesting the possibility that the activated T cells from patients with hypersensitivity are functional.
  
  
  CONCLUSIONS
  The expansion of type 0 and type 2 T cells phenotyped by IL-4 production may correlate with abacavir-associated hypersensitivity. The data suggest a cytokine bias that may facilitate B-cell differentiation and downregulate T-cell cytotoxic responses.
authors.affiliation: Department of Immunology, King's College London, UK.
authors.forename: Deborah
authors.initials: D
authors.lastname: King
authors.forename: Sarah
authors.initials: S
authors.lastname: Tomkins
authors.forename: Anele
authors.initials: A
authors.lastname: Waters
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Easterbrook
authors.forename: Linda M
authors.initials: LM
authors.lastname: Thurmond
authors.forename: Daren E
authors.initials: DE
authors.lastname: Thorborn
authors.forename: Francois
authors.initials: F
authors.lastname: Raffi
authors.forename: D Mike
authors.initials: DM
authors.lastname: Kemeny
authors.forename: Annapurna
authors.initials: A
authors.lastname: Vyakarnam
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology* / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear; D018655:Lymphocyte Count; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D007371:Interferon-gamma; D015847:Interleukin-4; D000099227:Abacavir