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.
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.
Authors: R Sharon Chinthrajah; Joseph D Hernandez; Scott D Boyd; Stephen J Galli; Kari C Nadeau Journal: J Allergy Clin Immunol Date: 2016-04 Impact factor: 10.793