Influence of bee venom immunotherapy on degranulation and leukotriene generation in human blood basophils.
BACKGROUND
Rapid clinical tolerance can be induced over several hours by very fast bee venom immunotherapy (VIT) protocols.


OBJECTIVE
To investigate the mechanisms underlying VIT we examined the changes of blood basophil responsiveness during VIT.


METHODS
Seven bee venom allergic patients with a history of severe systemic reactions after a bee sting were investigated. A cumulative dose of 111.1 micrograms bee venom (BV) was administered sc over 3.5 h under intensive care conditions according to an ultra-rush protocol. The release of histamine and the formation of leukotrienes in response to BV, major BV allergen Phospholipase A2 (PLA), IgE receptor cross-linking with the use of monoclonal antibodies against IgE and IgE receptor, as well as IgE independent activation in response to C5a were determined in vitro before and after ultra-rush VIT.


RESULTS
We demonstrated a decrease of total histamine in peripheral blood leucocytes just after VIT. Histamine release in response to all the stimuli used is not affected by ultra-rush VIT, if expressed as per cent release of total histamine. However, the absolute amount product released in response to stimulation was decreased, particularly with allergen (BV, PLA). We also found a significant reduction of LTC4 formation after VIT in samples stimulated with specific allergen (BV, PLA).


CONCLUSIONS
Blood basophils are a target for VIT, which induces impaired release of both preformed and newly generated mediators. However, we believe the basic mechanisms of rapid clinical tolerance induced by ultra-rush VIT remain to be investigated.
Jutel
M
M
Medical Division, Zieglerspital, Bern, Switzerland.
Müller
U R
UR
Fricker
M
M
Rihs
S
S
Pichler
W J
WJ
Dahinden
C
C
D000911:Antibodies, Monoclonal / Q000378:metabolism; D001491:Basophils / Q000187:drug effects* / Q000378:metabolism*; D001514:Bee Venoms / Q000627:therapeutic use*; D003594:Cytoplasmic Granules / Q000187:drug effects*; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D017997:Leukotriene C4 / Q000096:biosynthesis; D015289:Leukotrienes / Q000096:biosynthesis*; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D011485:Protein Binding / Q000276:immunology; D017455:Receptors, IgE / Q000378:metabolism; D013997:Time Factors
D000911:Antibodies, Monoclonal; D001514:Bee Venoms; D015289:Leukotrienes; D017455:Receptors, IgE; D017997:Leukotriene C4; D010741:Phospholipases A; D054467:Phospholipases A2