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The inhibition of kallikrein-bradykinin pathway may be useful in the reduction of allergic reactions during honeybee venom immunotherapy

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Author(s): Ervin Ç. Mingomataj | Alketa Bakiri

Journal: Iranian Journal of Medical Hypotheses & Ideas
ISSN 1735-9104

Volume: 3;
Start page: 10;
Date: 2009;
Original page

Keywords: Bradykinin antagonists | Hereditary angioedema | Honeybee venom immunotherapy | Kallikrein-bradykinin pathway | Systemic anaphylactic reactions

ABSTRACT
"nVenom immunotherapy (VIT) protects patients with hymenoptera venom anaphylaxis from subsequent potentially life-threatening reactions. The most important side effects during VIT are systemic anaphylactic reactions (SAR), which are more prevalent during honeybee VIT. Despite the demonstrated diversity with regard to venom compounds, previous publications did not mention the plausible reason that can justify the difference of SAR frequency between honeybee and wasps. On the other hand, pre-treatment with H1-blocking antihistamines reduces the frequency and intensity of local and mild systemic anaphylactic reactions during VIT, but not appropriately moderate adverse reactions such as abdominal pain or angioedematous reactions, which can occur more prevalently also during honeybee VIT. In contrast to hymenoptera venom (HV) anaphylaxis, these symptoms are very common during hereditary angioedema (HAE). In addition, in some patients who repeatedly experienced anaphylactic reactions during hyposensitization with HV are reported significantly lower renin, angiotensinogen I, and angiotensinogen II plasma levels. These facts may indicate that during honeybee VIT could be occurred a defective implication of renin-angiotensin system. This may be possible, because among hymenoptera, only the HV contains the antigen melittin, a potent kallikrein activator. These effects during honeybee VIT are similar to the HAE, because melittin-induced kallikrein activation on the first hand, as well as the implication of complement classical pathway during HAE on the second one, can lead both to increased bradykinin (BK) secretion, plasma extravasation, and therefore to the occurrence of angioedema and abdominal symptoms. Consequently, the clinical effectiveness of BK receptor and generator blockers such as icatibant, ecallantide or NPC 18884, shown recently during the treatment of HAE attacks and acetic acid-induced abdominal constrictions in mice, may lead to the hypothesis that a similar strategy could be useful during honeybee VIT in order to manage or prevent BK-induced symptoms such as angioedema and abdominal pain. However, the evaluation of this idea needs further appropriate experimental and clinical trials.

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