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Interleukin (IL)-4 induces production of cytokine-induced neutrophil chemoattractants (CINCs) and intercellular adhesion molecule (ICAM)-1 in lungs of asthmatic rats

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Summary

The present study aimed to examine the effect of interleukin (IL)-4 on neutrophil chemotaxis in airway inflammation in asthmatic rats and the possible mechanism. Male Wistar rats were intranasally instilled with recombinant rat (rr) IL-4 (rrIL-4) at different doses [2, 4 or 8 μg/animal, dissolved in 200 μL normal saline (NS)] or rrIL-4 at 4 μg/animal (dissolved in 200 μL NS). NS (200 μL) and LPS (6 mg/kg/animal, dissolved in 200 μL NS) were intranasally given respectively in the negative and positive control groups. Moreover, the asthmatic lung inflammation was induced in rats which were then intranasally treated with rrIL-4 (4 μg/animal) or LPS (6 mg/kg/animal). The normal rats treated with different doses of rrIL-4 and those asthmatic rats were sacrificed 6 h later. And animals instilled with rrIL-4 at 4 μg were sacrificed 6, 12 or 24 h later. The bronchoalveolar lavage fluid (BALF) and lungs were harvested for detection of leukocyte counts by Wright-Giemsa staining and lung histopathology by haematoxylin-eosin (HE) staining. The levels of cytokine-induced neutrophil chemoattractant (CINC)-1 and intercellular adhesion molecule (ICAM)-1 in BALF were determined by ELISA. Real-time PCR was used to measure the mRNA expression of CINCs (CINC-1, CINC-2α, CINC-2β, CINC-3) and ICAM-1 in lung tissues. The results showed that the intranasal instillation of IL-4 did not induce a recruitment of neutrophils in BALF in rats. However, IL-4 could increase the CINC-1 level in BALF in a dose-dependent manner at 6 h. But the mRNA expression levels of CINC-1, CINC-2α, CINC-2β, CINC-3 were not significantly increased in lungs of IL-4-treated rats relative to NS negative control group. Moreover, IL-4 was found to augment the mRNA expression of ICAM-1 in lungs and the ICAM-1 level in BALF at 6 h. However, the increase in CINC-1 and ICAM-1 levels in BALF of IL-4-treated asthmatic rats was not significantly different from that in untreated asthmatic rats. These findings indicate that IL-4 does not directly recruit neutrophils in the rat lungs, but it may contribute to airway neutrophilia through up-regulation of CINC-1 and ICAM-1.

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Authors and Affiliations

  1. Department of Respiratory Diseases and Critical Care Medicine, Tongji Hospital, Tonji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Ya-li Guo  (郭亚丽), Hong Huang  (黄 宏), Jian-ping Zhao  (赵建平) & Hui-juan Fang  (方慧娟)

  2. Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China

    Da-xiong Zeng  (曾大雄)

  3. Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, J2S 7C6, Canada

    Jean-pierre Lavoie

  4. Department of Respiratory Diseases and Critical Care Medicine, Henan Provincial People’s Hospital, Zhengzhou, 450003, China

    Ya-li Guo  (郭亚丽)

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  1. Ya-li Guo  (郭亚丽)
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  2. Hong Huang  (黄 宏)
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Correspondence to Hong Huang  (黄 宏).

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This project was supported by a grant from the National Natural Science Foundation of China (No. 30770945).

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Guo, Yl., Huang, H., Zeng, Dx. et al. Interleukin (IL)-4 induces production of cytokine-induced neutrophil chemoattractants (CINCs) and intercellular adhesion molecule (ICAM)-1 in lungs of asthmatic rats. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 33, 470–478 (2013). https://doi.org/10.1007/s11596-013-1144-5

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