Increased elastase and myeloperoxidase activity associated with neutrophil recruitment by IL-17 in airways in vivo☆,☆☆,★
Section snippets
Animals
We used pathogen-free male Sprague-Dawley rats (range 300-400 g, B&K Universal AB, Stockholm, Sweden). Animals were maintained on a standard laboratory food with water ad libitum. The experiments were approved by the Ethical Committee for Animal Studies at Göteborg University (DNo 134/95).
IT instillation of cytokines in vivo
Rats were anaesthetized with 1 mL/kg of a 3:2 mixture of ketamine hydrochloride (50 mg/mL, Parke-Davis Scandinavia, Sweden) and xylazine chloride (20 mg/mL, Bayer Sverige AB, Göteborg, Sweden) intramuscularly.
hIL-17 and mIL-17 versus BAL fluid neutrophil count
hIL-17 (1 μg) as well as mIL-17 (1 μg) induced a significant and similar increase of the BAL fluid neutrophil count (Table I) 6 hours after IT instillation.
Empty Cell BAL recovery volume (mL) Total cell (× 106/mL) Macrophage (× 106/mL) Neutrophil (× 106/mL) Eosinophil (× 106/mL) Lymphocyte (× 106/mL) Vehicle (n = 4) 17.7 ± 0.20 1.87 ± 0.24 1.21 ± 0.21 0.65 ± 0.19 0.003 ± 0.002 0.015 ± 0.009 hIL-17 (n = 4) 18.0 ± 0.08 4.71 ± 1.10 1.98
DISCUSSION
This study on BAL from rat airways in vivo shows that the increased number of neutrophils in BAL that is induced by hIL-17 IT is associated with an increased activity for ELA and MPO. Pretreatment with rat IL-1β enhances the hIL-17–induced ELA and MPO activity, without substantially increasing the BAL neutrophil count. Furthermore, hIL-17 exerts no direct activating effect on isolated rat neutrophils in vitro.
hIL-17 is a species heterologous cytokine that was used because recombinant rIL-17
Acknowledgements
We thank Carina Malmhäll for technical assistance.
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Supported by Göteborg University, the Persson Sisters’ Donation Fund at the Swedish Medical Agency, the Swedish Heart and Lung Foundation, the Swedish Medical Research Council (grants No. K97-04X-09-04-08A and U1268), the Swedish Medical Society, and the Vårdal Foundation.
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Reprint requests: Anders Lindén, MD, PhD, Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Göteborg University, Guldhedsgatan 10A, S-413 46 Gothenburg, Sweden.
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0091-6749/2000 $12.00 + 0 1/1/102543