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  • 1
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Ozone (O3) is a common air pollutant associated with adverse health effects. Asthmatics have been suggested to be a particularly sensitive group.Objective This study evaluated whether bronchial epithelial cytokine expression would differ between healthy and allergic asthmatics after ozone exposure, representing an explanatory model for differences in susceptibility.Methods Healthy and mild allergic asthmatic subjects (using only inhaled β2-agonists prn) were exposed for 2 h in blinded and randomized sequence to 0.2 ppm of O3 and filtered air. Bronchoscopy with bronchial mucosal biopsies was performed 6 h after exposure. Biopsies were embedded in GMA and stained with mAbs for epithelial expression of IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α, GRO-α, granulocyte–macrophage colony-stimulating factor (GM–CSF), fractalkine and ENA-78.Results When comparing the two groups at baseline, the asthmatic subjects showed a significantly higher expression of IL-4 and IL-5. After O3 exposure the epithelial expression of IL-5, GM–CSF, ENA-78 and IL-8 increased significantly in asthmatics, as compared to healthy subjects.Conclusion The present study confirms a difference in epithelial cytokine expression between mild atopic asthmatics and healthy controls, as well as a differential epithelial cytokine response to O3. This O3-induced upregulation of T helper type 2 (Th2)-related cytokines and neutrophil chemoattractants shown in the asthmatic group may contribute to a subsequent worsening of the airway inflammation, and help to explain their differential sensitivity to O3 pollution episodes.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: With the aim of investigating the distribution of T cells expressing different T-cell receptors (TCR) in the inflamed synovial tissue of rheumatoid arthritis patients, we have used the polymerase chain reaction to amplify TCR Vα and Vβ transcripts from synovial biopsies obtained by arthroscopy from patients with arthritis of variable duration. From each of nine patients a single biopsy was taken. Southern hybridization analysis of amplified products revealed extensive heterogeneity of TCR Vβ in most patients. On the other hand, restriction in Vα gene expression was seen in several patients. A highly restricted Vα repertoire was observed in all cases with arthritis of short duration. In addition, two of three samples of short duration yielded a more limited number of Vβ transcripts than the others. No conformity was, however, seen in usage of individual Vα and Vβ transcripts among the investigated patients. The present data thus demonstrate variability in synovial TCR expression between rheumatoid arthritis patients, but they also indicate a development towards greater diversity with increasing disease duration, implicating the necessity for careful choice of cases, preferentially selecting for early stages of disease, when further analysing rheumatoid synovial T cells for TCR usage as well as for antigen specificity.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Collagen-induced arthritis (CIA) is an experimental rat model sharing a number of features with human rheumatoid arthritis (RA). The model is associated with a proinflammatory (TH1) type of immune response and treatments with cytokines associated with TH2 immune responses are beneficial. Since agents with TH1-inducing properties, such as Freund's incomplete adjuvant (FIA), are necessary for disease induction, it is of interest to investigate whether an adjuvant with TH2-inducing properties affects CIA in a different way than does FIA. The authors studied arthritis development in DA rats after immunization with the TH2 stimulatory adjuvant alum adsorbed to rat collagen type II (CII) or collagen II fragments. Such treatments suppressed disease development both prophylactically and therapeutically. This beneficial effect of alum–CII immunization was associated with an increase in the IgG1 anti-CII antibody response as compared to untreated rats or rats pretreated with alum alone. Treatment with alum without the addition of collagen did not have any clinical effect. In addition, alum–CII treated rats had a significantly higher expression of IL-4 mRNA than untreated rats in the lymph nodes, 7 days after CIA induction. The authors suggest that alum–CII induces a TH2 immune response against rat CII which counteracts the development of CIA.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 54 (2001), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: T-cell mediated inflammatory joint diseases with similarities to rheumatoid arthritis (RA) can be triggered in arthritis-prone rat strains by intradermal injection of adjuvant oils. The pathogenesis of oil-induced arthritis (OIA) remains elusive, and a largely unresolved question is how the rat immune system responds to arthritogenic oils such as incomplete Freund's adjuvant (IFA). Here we report that IFA already induces increased plasma levels of the acute-phase reactants (APR) fibrinogen and α1-acid glycoprotein at day 4 postinjection (p.i). In contrast, no early responses were detected in the joints before infiltration of the T cells, which coincided with arthritis onset at 11–14 days post injection (d.p.i.) The infiltrating cells were possibly derived from draining lymph nodes (LN), which were hyperplastic and contained increased cell numbers from 4 days p.i. and onwards. The magnitude of the early increase in cell numbers and APR was regulated by non-major histocompatibility complex (MHC) genes, as determined by comparison between arthritis-susceptible DA rats and arthritis-resistant but MHC-identical LEW.1AV1 and PVG.1AV1 rats. Arthritis-prone DA rats developed a weak acute-phase response, suggesting that this systemic response may be counteracting disease. The DA rats also had the largest early increase in LN-cell numbers, suggesting that the LN hyperplasia is part of a disease pathway. The analysis of hyperplastic LN after in vivo labelling with bromodeoxyuridine (BrdU) revealed increased numbers and proportions of proliferating lymphocytes, including T cells. Furthermore, polymerase chain reaction (PCR)-analysis of LN cytokine mRNA revealed upregulation of interleukin (IL)-1β at 4 d.p.i. We conclude that adjuvant oil exposure triggers both systemic acute phase reactions and local activation of the peripheral lymphoid system. These responses are genetically regulated and may determine arthritis development and susceptibility.
    Type of Medium: Electronic Resource
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