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

TY - JOUR

T1 - Intracellular cytokines may model immunoregulation of abacavir hypersensitivity in HIV-infected subjects

AU - King, D

AU - Tomkins, S

AU - Waters, A

AU - Easterbrook, P J

AU - Thurmond, L M

AU - Thorborn, D E

AU - Raffi, F

AU - Kemeny, D M

AU - Vyakarnam, A

PY - 2005/5

Y1 - 2005/5

N2 - 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 dysiregulation, 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-γ in patients with abacavir-related hypersensitivity. Methods: Intracellular cytokines were enumerated in blood T cells by How 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 to with a frequency comparable with HIV-naive control cells, suggesting the possibility that the activated T cells from patients with hypersensitivity are functional. Conclusion: 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

AB - 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 dysiregulation, 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-γ in patients with abacavir-related hypersensitivity. Methods: Intracellular cytokines were enumerated in blood T cells by How 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 to with a frequency comparable with HIV-naive control cells, suggesting the possibility that the activated T cells from patients with hypersensitivity are functional. Conclusion: 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

U2 - 10.1016/j.jaci.2004.12.1140

DO - 10.1016/j.jaci.2004.12.1140

M3 - Article

SN - 1097-6825

VL - 115

SP - 1081

EP - 1087

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 5

ER -