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Intracellular cytokines may model immunoregulation of abacavir hypersensitivity in HIV-infected subjects.

The Journal of allergy and clinical immunology (2005-05-04)
Deborah King, Sarah Tomkins, Anele Waters, Philippa J Easterbrook, Linda M Thurmond, Daren E Thorborn, Francois Raffi, D Mike Kemeny, Annapurna Vyakarnam
ABSTRACT

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. Quantitation of the production of the type 2 IL-4 and the counterregulatory type 1 cytokine IFN-gamma in patients with abacavir-related hypersensitivity. 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. 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. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Human IgG (Fc specific)−Biotin antibody, Mouse monoclonal, clone HP-6017, purified from hybridoma cell culture
Sigma-Aldrich
Anti-Human IgM (μ-chain specific)−Biotin antibody produced in goat, affinity isolated antibody, buffered aqueous solution