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Published on: August 30, 2014
Mechanism for acute oral desensitization to antibiotics
1Department of Immunology, Chonbuk National University Medical School, Chonju, Korea.
Background:
Despite the widespread use of an acute oral desensitization procedure in patients with allergic reactions to a variety of antibiotics, the precise mechanism of this procedure is poorly understood.
Objective:
To investigate the mechanisms underlying acute oral desensitization to antibiotics.
Methods:
Using a murine model of active systemic anaphylaxis to penicillin V (Pen V), mice previously sensitized to Pen V were desensitized by oral feeding of Pen V. The dose was doubled every 15 min and five feedings were given. The achievement of acute oral desensitization was evaluated by induction of active systemic and active cutaneous anaphylaxis, and by measuring the plasma levels of platelet-activating factor and histamine. Antigen-specific serum IgE antibody (Ab) levels were determined by passive cutaneous anaphylaxis.
Results:
Mice fed more than 3 mg of cumulative dose of Pen V were completely protected from fatal systemic anaphylactic reaction and the desensitized state lasted approximately 1 h. Antigen-specific mast cell desensitization, but not hapten inhibition, consumption of IgE Abs, or depletion of mast cell mediators, occurred during acute oral desensitization.
Conclusions:
Acute oral desensitization to Pen V occurred in the mice, and antigen-specific mast cell desensitization was associated with the underlying mechanism for oral desensitization.
Insights
Acute oral antibiotic desensitization is effective, with a minimum dose protecting mice for an hour. This process involves antigen-specific mast cell desensitization, not IgE consumption.
Area of Science:
- Immunology
- Pharmacology
Background:
- Acute oral desensitization is widely used for antibiotic allergies but its mechanism is unclear.
- Understanding this mechanism is crucial for improving patient safety and treatment efficacy.
Purpose of the Study:
- To elucidate the immunological mechanisms behind acute oral antibiotic desensitization.
- To identify the key cellular and molecular events involved in this procedure.
Main Methods:
- A murine model of penicillin V-induced anaphylaxis was used.
- Mice were orally desensitized with escalating doses of penicillin V.
- Anaphylaxis induction, mediator levels (platelet-activating factor, histamine), and IgE levels were measured.
Main Results:
- A cumulative dose of over 3 mg of penicillin V conferred complete protection from anaphylaxis for approximately 1 hour.
- The primary mechanism identified was antigen-specific mast cell desensitization.
- Hapten inhibition, IgE consumption, and mediator depletion were not found to be the underlying mechanisms.
Conclusions:
- Acute oral desensitization to penicillin V was successfully achieved in a murine model.
- Antigen-specific mast cell desensitization is the key mechanism underlying acute oral antibiotic desensitization.
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