tacrolimus and Rhinitis--Allergic--Seasonal

Topics: Child; Cystic Fibrosis Transmembrane Conductance Regulator; Dermatitis, Atopic; Genetic Predisposition to Disease; Glucocorticoids; Humans; Hypersensitivity, Immediate; Immunosuppressive Agents; Incidence; Leukotriene Antagonists; Mutation; Rhinitis, Allergic, Seasonal; T-Lymphocytes; Tacrolimus

Allergies are frequently implicated in ophthalmologic practice. These typically benign allergies can be potentially severe for the ocular surface and have an impact in everyday life. We relate, through a case of keratoconjunctivitis involving 2 types of hypersensitivity, the various triggers and therapeutic choices to allow a more effective treatment.

Topics: Adult; Allergens; Animals; Azithromycin; Blepharitis; Cats; Dermatitis, Atopic; Desensitization, Immunologic; Dogs; Drug Therapy, Combination; Eosinophilia; Histamine Antagonists; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Intradermal Tests; Keratoconjunctivitis; Lubricant Eye Drops; Male; Pyroglyphidae; Rhinitis, Allergic, Seasonal; Tacrolimus

Pimecrolimus (Elidel, SDZ ASM 981) is an anti-inflammatory and immunomodulatory 33-epichloro-derivative of macrolactam ascomycin, with low potential for affecting systemic immune responses compared with other calcineurin inhibitors, cyclosporin A and tacrolimus. Despite numerous studies focused on the mechanism of pimecrolimus action on mast cells, only the single report has addressed pimecrolimus effects on other typical FcεRI-expressing cells, the basophils. Patients allergic to birch pollen (n = 20), hymenopteran venoms (n = 23) and 10 non-allergic volunteers were examined. Primary human basophils pre-treated or not with 0.5-50 μMol pimecrolimus were exposed to various concentrations of recombinant Bet v 1a allergen, bee or wasp venom extracts and anti-IgE for 20 min, and then examined for the expression of CD45, CD193, CD203c, CD63 and CD164 using flow cytometry. The externalization of basophil activation markers (CD63 and CD164) was equally inhibited through pimecrolimus in cells activated by recombinant pollen allergen, hymenopteran venom extracts and anti-IgE. Although the individual response rate was subject to strong variation, importantly, pre-treatment with pimecrolimus lowered the number of activated basophils in response to any of the stimuli in the basophils from all patients. The inhibition was concentration-dependent; approximately half of the basophils were inhibited in the presence of 2.5 mMol pimecrolimus. Pimecrolimus is a valuable new tool for the inhibition of hyper-reactive basophils in patients with pollen allergy and a history of anaphylactic reactions to bee or wasp venoms. Further research should address short-term use of pimecrolimus in vivo in a wide spectrum of allergic diseases.

Topics: Adult; Aged; Allergens; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Anti-Idiotypic; Basophils; Bees; Betula; Cells, Cultured; Humans; Hypersensitivity; Immunoglobulin E; Middle Aged; Receptors, IgE; Rhinitis, Allergic, Seasonal; Tacrolimus; Wasp Venoms; Wasps; Young Adult

A number of structurally different allergens trigger the release of mediators from basophils by cross-linking of IgE receptors. In this study, we analyzed the effects of cyclosporine A (CSA) and FK-506 on allergen-induced histamine release in human blood basophils obtained from birch- or grass-pollen-allergic donors (n = 12). Preincubation of basophils with CSA (0.003-3 microg/ml) or FK-506 (0.003-3 microg/ml) led to inhibition of histamine release induced by purified recombinant tree pollen allergens (r Bet v 1, r Bet v 2) and timothy grass pollen allergens (r Ph1 p 1, r Ph1 p 2, r Ph1 p 5). The effects of CSA and FK-506 were dose dependent, with IC50 values ranging between 0.03 and 0.3 microg/ml for both CSA and FK-506. Cyclosporine H, an inactive CSA analog, did not show any effect on allergen-induced histamine secretion. IgE dependency of the reaction was demonstrated in passive transfer experiments using highly enriched human basophils (> 95% pure) and specific IgE from a patient allergic to Bet v 2. In summary, our data show that CSA and FK-506 inhibit recombinant-allergen-induced histamine release from peripheral blood basophils in allergic donors.

Topics: Adult; Allergens; Asthma; Basophils; Conjunctivitis, Allergic; Cyclosporine; Female; Histamine Release; Humans; Immunization, Passive; Immunoglobulin E; Immunosuppressive Agents; In Vitro Techniques; Male; Middle Aged; Pollen; Rhinitis, Allergic, Seasonal; Tacrolimus