The topical glucocorticoids beclomethasone dipropionate and fluticasone propionate inhibit human T-cell allergen-induced production of IL-5, IL-3 and GM-CSF mRNA and protein.
BACKGROUND
T-cell production of eosinophil-active cytokines (IL-5, IL-3, GM-CSF) is thought to be fundamental to asthma pathogenesis. Inhaled aeroallergens may be one important stimulus for T-cell cytokine production in asthma.


OBJECTIVE
To compare the potency and efficacy of the topical anti-asthma glucocorticoids beclomethasone dipropionate (BDP) and fluticasone propionate (FP) in inhibiting allergen-driven peripheral blood T-cell proliferation and production of IL-3, IL-5 and GM-CSF mRNA and protein.


METHODS
Peripheral blood mononuclear cells from six atopic asthmatics sensitized to house dust mite (HDM) were cultured in the presence of HDM and serial dilutions of BDP or FP in vitro. Cellular proliferation (7 days) and culture supernatant cytokine concentrations (6 days) were measured by uptake of tritiated thymidine and ELISA, respectively. Cytokine mRNA expression (24 h) was measured in three subjects using a quantitative PCR technique.


RESULTS
Both BDP and FP inhibited allergen-induced T-cell proliferation, expression of IL-3, IL-5 and GM-CSF mRNA, and secretion of the corresponding proteins in a concentration-dependent fashion. FP was considerably more potent, but not more efficacious, in exerting these actions.


CONCLUSIONS
Both BDP and FP have the potential markedly to inhibit allergen-induced T-cell production of asthma-relevant cytokines. This activity is effected at the level of T-cell proliferation and cytokine gene transcription. These properties may be key features of the anti-asthma activity of these drugs. The greater potency of FP in vitro may be responsible for its greater clinical potency.
Powell
N
N
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
Till
S J
SJ
Kay
A B
AB
Corrigan
C J
CJ
D000287:Administration, Topical; D000730:Androstadienes / Q000494:pharmacology / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D039741:Antigens, Dermatophagoides; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001507:Beclomethasone / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D004391:Dust / Q000009:adverse effects; D000068298:Fluticasone; D005938:Glucocorticoids; D006023:Glycoproteins / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy* / Q000276:immunology; D007377:Interleukin-3 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D039741:Antigens, Dermatophagoides; D016207:Cytokines; D004391:Dust; D005938:Glucocorticoids; D006023:Glycoproteins; D007377:Interleukin-3; D015848:Interleukin-5; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000068298:Fluticasone; D001507:Beclomethasone