Interleukin-17-producing T-helper cells and related cytokines in human airways exposed to endotoxin

• Published in: The European respiratory journal Vol. 36; no. 5; pp. 1155 - 1164
• Main Authors: GLADER, P, SMITH, M. E, MALMHÄLL, C, BALDER, B, SJÖSTRAND, M, QVARFORDT, I, LINDEN, A
• Format: Journal Article
• Language: English
• Published: Leeds Maney 01.11.2010
• Subjects: Alveoli; Biological and medical sciences; Bronchoalveolar Lavage Fluid - immunology; Bronchoscopy; Dermatologi och venereologi; Dermatology and Venereal Diseases; Endotoxins - toxicity; Flow Cytometry; Humans; Interleukin-17 - genetics; Interleukin-17 - metabolism; Interleukin-22; Interleukins - genetics; Interleukins - metabolism; Macrophages, Alveolar - cytology; Macrophages, Alveolar - immunology; Medical sciences; Microbiology in the medical area; Mikrobiologi inom det medicinska området; Neutrophils - cytology; Neutrophils - immunology; Nuclear Receptor Subfamily 1, Group F, Member 1 - genetics; Nuclear Receptor Subfamily 1, Group F, Member 1 - metabolism; Pneumology; Receptor Tyrosine Kinase-like Orphan Receptors - genetics; Receptor Tyrosine Kinase-like Orphan Receptors - metabolism; RNA, Messenger - metabolism; Th17 Cells - cytology; Th17 Cells - immunology; Th17 Cells - metabolism; Human; Toxin; Immunological investigation; Bronchoalveolar lavage; Cytokine; T-Lymphocyte; Endotoxin; Interleukin 17; T-helper 17 cells; Pneumology
• ISSN: 0903-1936; 1399-3003; 1399-3003
• DOI: 10.1183/09031936.00170609

Previous studies on mouse models have indicated that interleukin (IL)-17 and IL-17-producing T-helper (Th) cells are important for pulmonary host defence against Gram-negative bacteria. Human correlates to these findings have not yet been demonstrated. The aim of the present study was to determine whether or not IL-17-producing Th cells are present and whether IL-17 and other Th17-associated cytokines are involved in the immunological response to endotoxin in human airways. Segmental exposure to endotoxin and contralateral exposure to vehicle were performed in the lungs of healthy volunteers, with subsequent bronchoalveolar lavage 12 or 24 h after exposure to study local changes in cytokines and inflammatory cells. Endotoxin exposure increased concentrations of IL-17, IL-22 and their downstream effector molecules, human β-defensin-2 and IL-8/CXC chemokine ligand 8, in bronchoalveolar lavage fluid. Th cells with the capacity to produce IL-17 were found among the bronchoalveolar lavage cells, and expression of IL-17 mRNA correlated with expression of the transcription factor, retinoic-acid-receptor-related orphan receptor C variant 2. Moreover, endotoxin increased the numbers of neutrophils, macrophages and IL-17-producing T-cells, as well as the concentration of the Th17-regulating cytokines, IL-21 and IL-23. In conclusion, IL-17-producing Th cells are present, and IL-17, as well as other Th17-associated cytokines, is involved in the immunological response to endotoxin in human airways.