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IL-4 and IFN-γ mRNA Induction in Human Peripheral Lymphocytes Specific for β-Lactam Antibiotics in Immediate or Delayed Hypersensitivity Reactions

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Abstract

β-Lactam antibiotics elicit CD4+ and CD8+ T-cell-mediated immune responses that play a central role in allergic reactions. However, the involvement of a type 1- (Th1 or Tc1) or a type 2-like (Th2 or Tc2) differentiation in drug allergy remains unclear. We investigated the expression of interleukin 4 (IL-4) and interferon gamma (IFN-γ) mRNA by quantitative reverse transcription and polymerase chain reaction (RT-PCR) in patient-derived peripheral blood lymphocytes following specific in vitro stimulation. Samples were collected from a total of 19 patients who had developed immediate or delayed clinical manifestations of hypersensitivity to β-lactam and from 11 control subjects. Peripheral blood mononuclear cells (PBMCs) were stimulated with either free antibiotics or antibiotic–human serum albumin (HSA) conjugates. Specific induction of IFN-γ mRNA expression was observed in 11 of 11 allergic patients with immediate reactions, in 6 of 8 patients with delayed reactions, and in 4 of 11 control subjects. IL-4 mRNA expression was induced in 5 of 11 allergic individuals with immediate reactions but in none of the 8 patients with delayed responses and none of the 11 control subjects. IL-4 mRNA expression was only induced following activation with free drugs, while IFN-γ mRNA expression was predominantly induced in CD4+ T cells following stimulation with HSA-conjugated drugs. Immediate-type hypersensitivity to β-lactams was not associated with a pure type 2-like response when PBMCs were specifically stimulated in vitro: Some patients with well-documented history of β-lactam-induced immediate allergic reaction showed a high IFN-γ response. Contact dermatitis involved Tc1 and Th1 cells and other delayed hypersensitivity reactions to β-lactams were restricted to Th1 responses.

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Authors and Affiliations

  1. Facult´e de Pharmacie, INSERM U461, 5 rue JB Cl´ement, 92296, Ch^atenay-Malabry, France

    Isabelle Gaspard, Nicolas Bachot, Saadia Kerdine, Jacques Bertoglio, Marc Pallardy & Herv´e Lebrec

  2. Unit´e d'Allergologie de l'Institut Pasteur, 75015, Paris, France

    Marie-Th´er`ese Guinnepain & J´erome Laurent

Authors
  1. Isabelle Gaspard
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  2. Marie-Th´er`ese Guinnepain
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  3. J´erome Laurent
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  4. Nicolas Bachot
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  5. Saadia Kerdine
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  6. Jacques Bertoglio
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  7. Marc Pallardy
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  8. Herv´e Lebrec
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Gaspard, I., Guinnepain, MT., Laurent, J. et al. IL-4 and IFN-γ mRNA Induction in Human Peripheral Lymphocytes Specific for β-Lactam Antibiotics in Immediate or Delayed Hypersensitivity Reactions. J Clin Immunol 20, 107–116 (2000). https://doi.org/10.1023/A:1006682413834

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