ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00660.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryThe rationale for using topical corticosteroids in the treatment of allergic rhinitis is that high drug concentrations can be achieved at receptor sites in the nasal mucosa, with minimal risk of systemic adverse effects. Topical corticosteroids have been demonstrated to reduce the number of Langerhans' cells (or their markers) in the nasal mucosa, and this is thought to attenuate antigen presentation. T lymphocytes have been identified as being significant in orchestrating the immune‐inflammatory response, particularly the TH2cells, which represent an important target for topical corticosteroids. TH2cell‐evoked mast cells and basophils are the sole producers of histamine, a mediator of major importance for rhinitis symptoms. Several studies have shown that the increased number of mast cells and basophils in the epithelium following antigen challenge/exposure, are markedly reduced by topical corticosteroids. Furthermore, the number of eosinophils, an important morphological marker of allergic rhinitis, can be profoundly reduced by treatment with topical corticosteroids. The rationale for topical treatment is strengthened by evidence of inhibition of cytokine release from surface epithelial cells, resulting in reduced recruitment and activation of mast cells, basophils, and eosinophils, which may be attributed to the high drug concentration achieved in epithelial cells. Ongoing inflammation in the mucous membrane is indicated by entry of plasma into the nasal lumen which subsides with the anti‐inflammatory efficacy of topical corticosteroids. In contrast to anlihistamine therapy, which has little effect on nasal blockage, pretreatment with topical corticosteroids results in almost complete attenuation of late‐phase symptoms including nasal blockage, and moderate efficacy in early phase symptoms. Clearly, the spectrum of anti‐inflammatory activity afforded by topical corticosteroid therapy is of clinical significance in reducing the three major symptoms of allergic rhinitis — sneezing, watery rhinorrhoea and nas

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00652.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00661.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00662.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb01137.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryThe pathogenesis of allergic rhinitis is complex, involving not only histamine and mast cell‐derived tryptase, but also eosinophil‐ and neutrophil‐derived mediators, cytokines, and intercellular cell adhesion molecules (ICAM‐1). It is surprising that antihistamines, which block only one component of the process, have proved so effective in the management of allergic rhinitis. Research has therefore focused on whether antihistamines have additional pharmacological activities.In vitrostudies have shown that high concentrations of second generation antihistamines can block inflammatory mediator release from basophils and mast cells, and reduce ICAM‐1 expression in epithelial cell lines.In vivostudies have also shown an effect on the allergen‐induced inflammatory reaction; both oral and intranasal antihistamines cause a reduction in nasal symptoms and inflammatory cell influx. Oral terfenadine and cetirizine and intranasal levocabastine and azelastine have also demonstrated a lowering of ICAM‐1 expression on epithelial cells. With regard to clinical efficacy, topical levocabastine (0.5mg/mL eye drop solution and 0.5 mg/mL nasal spray) was shown to be more effective than oral terfenadine (60mg twice daily) in relieving ocular itch (P=0.02) and reducing nasal symptoms in allergic rhinoconjunctivitis. In a further study. levocabastine eye drops were as effective and well tolerated as sodium cromoglycate in seasonal allergic rhinitis. Intranasal azelastine (0.28mg twice daily) showed a trend for superior relief of rhinorrhoea and nasal obstruction compared with oral terfenadine (60mg twice daily). In addition, intranasal azelastine (0.28 mg twice daily) resulted in significant reductions in sneezing, nasal obstruction, rhinorrhoea and itching in perennial rhinitis, compared with the lower efficacy of beclomethasone dipropionate (0.1 mg twice daily). As well as benefits in efficacy, topical administration is associated with improved safety. Some antihistamines, particularly those metabolized in the liver, are associated with occasional reports of severe side‐effects. It is therefore logical to administer antihistatnines directly to t

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00653.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00051.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb01138.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00663.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundSelected cytokines produced by allergen specific CD4+T cells from atopic individuals contribute to both the specific and non‐specific effector mechanisms of the allergic itnmune response. The chemokine family of cytokines and tumour necrosis factor (TNF)‐α are leucocyte regulatory and proinflanimatory molecules. The chemokines include interleukin (IL)‐8 and the RANTES/SIS cytokines.ObjectiveThere has been no systematic survey of chemokine production in T‐cell subtypes. Because of their wide range of biological properties, it might be expected that they would be closely regulated by T cells. This paper illustrates one way (through the characterization of T‐cell clones) these questions might be addressed.MethodsNorthern blot analysis was used to quantitate steady state transcription of selected cytokine genes and enzyme linked imtiiunosorbent assay (ELISA) was used to quantitate soluble product.ResultsmRNA expression of the chemokines (IL‐8, HuMIP‐1α and HuMIP‐1β) and TNFα is upregulated in TH2‐like cloned house dust mite reactive human CD4+T cells under conditions of activation and during the induction phase of anergy. Although the development of anergy superinduces mRNA for both IL‐8 and TNFα. protein production is low compared with that released during activation. In contrast. RANTES, a chemoattractant for CD4+/CD45RO+memory T cells, eosinophils and basophils, is constitutively expressed at the RNA level by the T cells and not modulated by signals of activation and anergy induction. The production of IL‐2, IL‐4 and IL‐5 mRNA and proteins during the induction of anergy peaks at 2h after stimulation, whereas the kinetics following activation of the T cells is delayed in comparison.ConclusionThese data show that the induction of the anergic state coincides with post‐transcriptional regulation of selected cytokine genes. Further study of these phenomena will impact on our understanding of the mechanisms of induction of anergy and the regulation of allergic imm

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00052.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY