Mite antigen-induced IL-4 and IL-13 production by basophils derived from atopic asthma patients.
BACKGROUND
There is increasing evidence for the role of basophils in the pathogenesis of atopic diseases such as bronchial asthma, atopic dermatitis and atopic rhinitis. Recently, it has been reported that basophils derived from healthy donors produce the immunoregulatory cytokines interleukin (IL)-4 and IL-13 after cross-linking of cell surface IgE. In addition to well-known inflammatory mediators, such as histamine and leukotriene C4. these cytokines produced by basophils are also considered to be associated with atopic diseases.


OBJECTIVE
Our first objective was to determine whether or not mite-sensitive atopic asthmatic basophils produce IL-4 and IL-13 in response to mite antigens. Our second objective was to investigate the relationship between antigen-specific or nonspecific IgE in the serum and the production of these cytokines in order to determine the association of basophil-derived cytokines with the pathogenesis of atopic asthma. Our final objective was to study how production of these cytokines could be regulated by some anti-asthma drugs.


METHODS
Basophils were purified from peripheral venous blood of 67 atopic asthma patients with elevated RAST for the house dust mite. Cells were stimulated with mite antigens for 6 hours and then IL-4 and IL-13 levels in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA).


RESULTS
Mite-sensitive asthmatic basophils produced IL-4 and IL-13 when stimulated with mite antigens. Mite-induced IL-4 production peaked at 6 hours after the stimulation. whereas IL-13 production continued up to 24 hours. The higher the concentration of mite-specific IgE but not total IgE released in the serum, the more IL-4 and IL-13 were produced by basophils in response to mite antigens. The production of these cytokines was significantly suppressed by the anti-asthma drugs theophylline (IL-4, p<0.001, n=6; IL-13, p<0.001, n=10) and dexamethasone (IL-4, p<0.001, n=15; IL-13, p<0.001, n=10).


CONCLUSIONS
Mite-antigen-induced IL-4 and IL-13 production by basophils derived from mite-sensitive asthma patients was associated with the concentration of mite-specific IgE and may play an important role in the pathogenesis of atopic asthma. The inhibitory effect of dexamethasone and theophylline on allergic inflammation may be due to the inhibition of IL-4 and IL-13 production not only by T cells but also by basophils.
Shimizu
Y
Y
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Shichijo
M
M
Hiramatsu
K
K
Takeuchi
M
M
Nagai
H
H
Takagi
K
K
D000287:Administration, Topical; D000328:Adult; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000941:Antigens / Q000008:administration & dosage / Q000494:pharmacology; D039741:Antigens, Dermatophagoides; D001249:Asthma / Q000097:blood* / Q000276:immunology / Q000473:pathology; D001491:Basophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001993:Bronchodilator Agents / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids; D006023:Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood* / Q000276:immunology / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D018793:Interleukin-13 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D007700:Kinetics; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008925:Mites / Q000276:immunology*; D013806:Theophylline / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000941:Antigens; D039741:Antigens, Dermatophagoides; D001993:Bronchodilator Agents; D005938:Glucocorticoids; D006023:Glycoproteins; D018793:Interleukin-13; D015847:Interleukin-4; D007073:Immunoglobulin E; D003907:Dexamethasone; D013806:Theophylline