Recombinant human diamine oxidase prevents histamine-induced hypoxia, shock and death in guinea pigs.

BACKGROUND AND

OBJECTIVE

Histamine is the principal effector of anaphylaxis, and circulating levels correlate well with symptom severity in Hymenoptera venom-induced anaphylaxis. Adrenaline, the recommended first-line therapy, does not neutralize histamine and may cause relevant adverse effects. Recombinant human diamine oxidase (rhDAO), engineered with a mutated heparin-binding motif, exhibits improved pharmacokinetics and rapid histamine-degrading activity. The primary aim of this study was to evaluate whether prophylactic or particularly therapeutic rhDAO prevents or reduces histamine-induced shock compared with adrenaline in guinea pigs.

METHODS

Guinea pigs received subcutaneous histamine (1 mg/kg) with or without intramuscular adrenaline or intravenous rhDAO (2-8 mg/kg). Mean arterial pressure, heart rate, and arterial oxygen partial pressure (PaO₂) were monitored. Plasma histamine and rhDAO levels were measured.

RESULTS

Histamine injection raised plasma levels above 200 ng/ml and consistently induced shock with 42% mortality. Prophylactic and therapeutic rhDAO completely degraded circulating histamine, reduced shock incidence from 100% to 0% at the highest doses, shortened tachycardia, improved PaO₂ and decreased mortality. Intramuscular adrenaline (0.005 or 0.01 mg/kg) did not improve hemodynamics, oxygenation or survival.

CONCLUSION

Recombinant hDAO prevented and treated histamine-induced shock and hypoxia, whereas adrenaline was ineffective. These findings support clinical development of rhDAO for life-threatening histamine-mediated conditions, including anaphylaxis.