BACKGROUND. In atopic asthma, activated T helper lymphocytes are present in bronchial-biopsy specimens and bronchoalveolar-lavage (BAL) fluid, and their production of cytokines may be important in the pathogenesis of this disorder. Different patterns of cytokine release are characteristic of certain subgroups of T helper cells, termed TH1 and TH2, the former mediating delayed-type hypersensitivity and the latter mediating IgE synthesis and eosinophilia. The pattern of cytokine production in atopic asthma is unknown. METHODS. We assessed cells obtained by BAL in subjects with mild atopic asthma and in normal control subjects for the expression of messenger RNA (mRNA) for interleukin-2, 3, 4, and 5, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interferon gamma by in situ hybridization with 32P-labeled complementary RNA. Localization of mRNA to BAL T cells was assessed by simultaneous in situ hybridization and immunofluorescence and by in situ hybridization after immunomagnetic enrichment or depletion of T cells. RESULTS. As compared with the control subjects, the subjects with asthma had more BAL cells per 1000 cell that were positive for mRNA for interleukin-2 (P less than 0.05), 3 (P less than 0.01), 4 (P less than 0.001), and 5 (P less than 0.001) and GM-CSF (P less than 0.001). There was no significant difference between the two groups in the number of cells expressing mRNA for interferon gamma. In the subjects with asthma, mRNA for interleukin-4 and 5 was expressed predominantly by T lymphocytes. CONCLUSIONS. Atopic asthma is associated with activation in the bronchi of the interleukin-3, 4, and 5 and GM-CSF gene cluster, a pattern compatible with predominant activation of the TH2-like T-cell population.
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National Heart and Lung Institute, London, United Kingdom.
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Zimmermann, N., Mishra, A., King, N. E., Fulkerson, P. C., Doepker, M. P., Nikolaidis, N. M., Kindinger, L. E., Moulton, E. A., Aronow, B. J., Rothenberg, M. E.
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Webb, D. C., Matthaei, K. I., Cai, Y., McKenzie, A. N. J., Foster, P. S.
(2004). Polymorphisms in IL-4R{alpha} Correlate with Airways Hyperreactivity, Eosinophilia, and Ym Protein Expression in Allergic IL-13-/- Mice. J. Immunol.
172: 1092-1098
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Brightling, C. E., Pavord, I. D., Flood-Page, P. T., Menzies-Gow, A. N., Kay, A. B., Robinson, D. S.
(2004). Eosinophils in Asthma and Airway Hyperresponsiveness. Am. J. Respir. Crit. Care Med.
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Sasaki, Y., Mita, H., Toyota, M., Ishida, S., Morimoto, I., Yamashita, T., Tanaka, T., Imai, K., Nakamura, Y., Tokino, T.
(2003). Identification of the Interleukin 4 Receptor {alpha} Gene as a Direct Target for p73. Cancer Res.
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Kang, H.-S., Blink, S. E., Chin, R. K., Lee, Y., Kim, O., Weinstock, J., Waldschmidt, T., Conrad, D., Chen, B., Solway, J., Sperling, A. I., Fu, Y.-X.
(2003). Lymphotoxin Is Required for Maintaining Physiological Levels of Serum IgE That Minimizes Th1-mediated Airway Inflammation. J. Exp. Med.
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Sawicka, E., Zuany-Amorim, C., Manlius, C., Trifilieff, A., Brinkmann, V., Kemeny, D. M., Walker, C.
(2003). Inhibition of Th1- and Th2-Mediated Airway Inflammation by the Sphingosine 1-Phosphate Receptor Agonist FTY720. J. Immunol.
171: 6206-6214
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Chen, E., Fisher, E. B., Bacharier, L. B., Strunk, R. C.
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Nikolaidis, N. M., Zimmermann, N., King, N. E., Mishra, A., Pope, S. M., Finkelman, F. D., Rothenberg, M. E.
(2003). Trefoil Factor-2 Is an Allergen-Induced Gene Regulated by Th2 Cytokines and STAT6 in the Lung. Am. J. Respir. Cell Mol. Bio.
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Sandler, N. G., Mentink-Kane, M. M., Cheever, A. W., Wynn, T. A.
(2003). Global Gene Expression Profiles During Acute Pathogen-Induced Pulmonary Inflammation Reveal Divergent Roles for Th1 and Th2 Responses in Tissue Repair. J. Immunol.
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Jeffery, P., Holgate, S., Wenzel, S.
(2003). Methods for the Assessment of Endobronchial Biopsies in Clinical Research: Application to Studies of Pathogenesis and the Effects of Treatment. Am. J. Respir. Crit. Care Med.
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Legg, J. P., Hussain, I. R., Warner, J. A., Johnston, S. L., Warner, J. O.
(2003). Type 1 and Type 2 Cytokine Imbalance in Acute Respiratory Syncytial Virus Bronchiolitis. Am. J. Respir. Crit. Care Med.
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Chiang, D.-J., Ye, Y.-L., Chen, W.-L., Lee, Y.-L., Hsu, N.-Y., Chiang, B.-L.
(2003). Ribavirin or CpG DNA Sequence-Modulated Dendritic Cells Decrease the IgE Level and Airway Inflammation. Am. J. Respir. Crit. Care Med.
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