Influence of bee venom immunotherapy on degranulation and leukotriene generation in human blood basophils.
ABSTRACT Rapid clinical tolerance can be induced over several hours by very fast bee venom immunotherapy (VIT) protocols.
To investigate the mechanisms underlying VIT we examined the changes of blood basophil responsiveness during VIT.
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.
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).
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.
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ABSTRACT: Insect venom is a poisonous substance that contains a complex mixture of certain proteins, enzymes, small peptides, certain inorganic elements and acids. These venom components are responsible for multiple pharmacological effects in different organisms and act like toxins. These act at cellular level and break the normal barrier to leak out molecules across the cell membrane and forms ion channels by attaching themselves to the membrane surface. Venom allergens cause immuno-stimulation of body tissues and show strong T cell responses in hypersensitive patients and signify the production of allergen specific IgE antibodies and generate anaphylactic reactions.. These also trigger a cascade of mediators including histamine, leucotrienes, and platelet activating factors, enzymes and peptides. Venom toxins make fast release of certain chemicals i.e. serotonin, kinins, postaglandins and leukotrienes that results in visible clinical symptoms related to paralysis, inflammation, swelling and itching. Insect venom toxins elevate the level of blood sugar, lactate, glucagon and cortisol and cause massive destruction of RBCs and nerve cells. Besides this, insect venom possess highly potent short peptides, which act upon ion channels of excitable cells and inhibit the activity of important metabolic enzymes like ACP ALP, GPT, GOT, LDH, AChE and Creatinine phosphokinase. Melittin is a short peptide that shows cytotoxicity and cause intra-vascular hemolysis of RBCs, lecocytes, platelets and vascular endothelium. It is highly basic and inserts itself into the phospholipid bi-layer of cell membranes. It in conjugation with PLA2 causes active pancreatitis and rhabdomyolysis in patients. Indeed, it appears that peptide toxins are strong ion channel blockers, which selectively act on various ion channels. This review aims to emphasize use of toxin specific immunoglobulin in for immunotherapy of patients to detoxify the effect of venom toxins. Immunotherapy contributes to decrease the number of mast cells, do activation of eosinophils, and induce T cell tolerance to the venom allergen. It subside the toxic effects of venom toxins and much ably revert the enzyme activity
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ABSTRACT: SUMMARY After a systemic allergic reaction, the use of an emergency medical kit should clearly explained to the patient. I.m. injected epinephrine is the treatment of choice for acute anaphylaxis. Venom immunotherapy (VIT) is indicated both in children and adults with a history of severe systemic reactions and documented sensitisation to the respective insect. As for systemic, non life-threatening reactions other factors may influence the decision to initiate VIT. The efficacy of VIT was demonstrated in three prospective controlled and a number of prospective uncontrolled studies. Most patients with mild to moderate anaphylactic symptoms and positive skin tests remain protected even years after VIT lasting three to five years has been discontinued. Longer term or lifelong treatment should be considered in high-risk patients.