Comparison of local cytokine gene expression and the distribution of eosinophils and CD4-positive cell subsets in the paranasal sinus mucosa between atopic and non-atopic subjects

Authors

  • Sachio Takeno,

    1. Department of Otolaryngology, Head and Neck Surgery, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University and
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  • Koji Yajin,

    1. Department of Otolaryngology, Head and Neck Surgery, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University and
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  • Atsushi Hisayuki,

    1. Department of Otolaryngology, Head and Neck Surgery, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University and
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  • Kyosuke Furukido,

    1. Department of Otolaryngology, Head and Neck Surgery, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University and
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  • Katsuhiro Hirakawa,

    1. Department of Otolaryngology, Head and Neck Surgery, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University and
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  • Takashi Ishino,

    1. Department of Otolaryngology, Head and Neck Surgery, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University and
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  • Rika Osada,

    1. Department of Otolaryngology, Head and Neck Surgery, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University and
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  • Tomoyuki Ogawa,

    1. Department of Otolaryngology, Head and Neck Surgery, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University and
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  • Hiroko Kawamoto

    1. Department of Otolaryngology, Head and Neck Surgery, Hiroshima Prefecture Hospital, Hiroshima, Japan
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  • This paper was presented, in part, at the 6th International Academic Conference on Immuno- & Molecular Biology in Otorhinolaryngology, 17−20 October 2002, Jeju Island.

Dr Sachio Takeno, Department of Otolaryngology, Hiroshima University School of Medicine, Kasumi 1-2-3, Minami-ku, Hiroshima-city, Hiroshima 734-8551, Japan. Email: takeno@hiroshima-u.ac.jp

Abstract

Background:  The role of Th2 type cytokines in the persistence of chronic rhinosinusitis, especially that induced by non-infectious inflammatory causes, has been noted. However, the original cause of sinus eosinophilia remains unclear and whether the presence of allergic rhinitis (AR) may be a risk factor has been an issue of debate. In the present study, we examined cytokine expression and the distribution of CD4-positive cell subsets in the paranasal sinus mucosa of patients with chronic sinusitis.

Methods:  A total of 133 sinusitis patients was examined. Patients were subdivided into four groups based on the presence of AR and the degree of local eosinophil infiltration. The expression of granulocyte− macrophage colony stimulating factor (GM-CSF), interleukin (IL)-5, IL-8, IL-16, eotaxin and interferon (IFN)-γ mRNA was detected by reverse transcription− polymerase chain reaction. Immunohistochemical localization of CD4-, CXCR3- and CCR4-positive cells in the same specimens was quantitatively analyzed using a laser scanning confocal microscope.

Results:  The group of non-AR patients with low eosinophilia (the AR(−)Eo(−) group) only showed an increase in IFN-γ mRNA expression. In contrast, the other three groups showed similar cytokine profiles, with high expression levels for GM-CSF, IL-5 and eotaxin mRNA. The total number of CD4+ cells was also increased in these three groups. The density of CCR4-positive CD4+ cells was significantly higher in groups with high eosinophilia, irrespective of the presence of AR. As a result, the CXCR3+/CCR4+ cell ratio in the AR(−)Eo(−) group was significantly increased compared with the other three groups.

Conclusions:  These results indicate that high expression of Th2-type cytokines concomitant with the infiltration of a predominant number of CD4+ cells and their Th2 subsets play a role in the pathogenesis of eosinophil inflammation in sinus mucosa. In addition, the finding that some of the non-atopic patients also shared Th-2 type immune responses provides support for the concept of chronic sinusitis as a Th2-mediated disease process.

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