calcimycin and Food-Hypersensitivity

Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, and food additives (FAs) may exacerbate allergic symptoms in patients with chronic idiopathic urticaria and food-dependent exercise-induced anaphylaxis (FDEIA). Augmentation of histamine release from human mast cells and basophils by those substances is speculated to be the cause of exacerbated allergic symptoms. We sought to investigate the mechanism of action of aspirin on IgE-mediated histamine release.. The effects of NSAIDs, FAs or cyclooxygenase (COX) inhibitors on histamine release from human basophils concentrated by gravity separation were evaluated.. Benzoate and tartrazine, which have no COX inhibitory activity, augmented histamine release from basophils similar to aspirin. In contrast, ibuprofen, meloxicam, FR122047 and NS-398, which have COX inhibitory activity, did not affect histamine release. These results indicate that the augmentation of histamine release by aspirin is not due to COX inhibition. It was observed that aspirin augmented histamine release from human basophils only when specifically activated by anti-IgE antibodies, but not by A23187 or formyl-methionyl-leucyl-phenylalanine. When the IgE receptor signaling pathway was activated, aspirin increased the phosphorylation of Syk. Moreover, patients with chronic urticaria and FDEIA tended to be more sensitive to aspirin as regards the augmentation of histamine release, compared with healthy controls.. Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.

Topics: Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Asthma, Exercise-Induced; Basophils; Benzoates; Calcimycin; Cell Degranulation; Cells, Cultured; Child; Chronic Disease; Cyclooxygenase Inhibitors; Enzyme Activation; Female; Food Hypersensitivity; Histamine Release; Humans; Immunoglobulin E; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; Phosphorylation; Protein-Tyrosine Kinases; Signal Transduction; Syk Kinase; Tartrazine; Urticaria; Young Adult

Allergic reactions to food can involve diarrhea, vomiting, nausea and abnormal pain. PG102 has previously been shown to control various factors involved in allergy pathogenesis, including IgE and various Th1 and Th2 cytokines, in vivo as well as in vitro [Park EJ, et al.: J Allergy Clin Immunol 2005;116:1151-1157; Park EJ, et al.: J Invest Dermatol 2007;127:1154-1160]. These data indicate that PG102 might have antiallergic effects on allergic diarrhea. Here, we investigated whether PG102 could prevent allergic diarrhea in the murine ovalbumin (OVA)-induced allergic diarrhea model.. BALB/c mice were orally treated with PG102, dexamethasone or water for 9 days on a daily basis, followed by subcutaneous injection with OVA on day 0. Animals were orally administrated with OVA from day 7, 3 times a week, over a period of approximately 20 days. Incidence of diarrhea, serum, OVA-restimulated splenocytes and lamina propria lymphocytes were analyzed.. Oral administration of PG102 could suppress the incidence of diarrhea in a murine allergic diarrhea model. The amelioration of allergic diarrhea by PG102 was accompanied with the inhibition of mast cell infiltration into the large intestine. The serum level of IgE, IL-6 and MCP-1 was decreased in PG102-treated mice. When splenocytes were isolated from respective groups and cultured in the presence of OVA, cells from PG102-administrated animals produced lesser amounts of IL-6 and MCP-1.. PG102 has the potential to be used as a preventive for food allergic diseases.

Topics: Actinidia; Animals; Calcimycin; Cell Movement; Chemokine CCL2; Dexamethasone; Diarrhea; Disease Models, Animal; Female; Food Hypersensitivity; Immunoglobulin E; Interleukin-10; Interleukin-4; Interleukin-6; Intestine, Large; Lymphocytes; Mast Cells; Mice; Mice, Inbred BALB C; Mucous Membrane; Ovalbumin; Plant Extracts; Rats; Spleen