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Open Access Research article

Insulin modulates cytokine release and selectin expression in the early phase of allergic airway inflammation in diabetic rats

Joilson O Martins13*, Carlos AL Campos1, José WMC Cruz1, Simone Manzolli1, Venâncio AF Alves2, Elcio O Vianna4, Sonia Jancar3 and Paulina Sannomiya1

Author Affiliations

1 Institute of Heart (InCor), LIM-11, University of São Paulo Medical School, Av. Dr. Arnaldo, 455 - São Paulo/SP - 01246903 - Brazil

2 Department of Pathology, University of São Paulo Medical School, Av. Dr. Arnaldo, 455 - São Paulo/SP - 01246903 - Brazil

3 Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1730 - São Paulo/SP - Brazil

4 Department of Medicine, Medical School of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900 - Ribeirão Preto/SP - 14049-900 - Brazil

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BMC Pulmonary Medicine 2010, 10:39  doi:10.1186/1471-2466-10-39

Published: 28 July 2010

Abstract

Background

Clinical and experimental data suggest that the inflammatory response is impaired in diabetics and can be modulated by insulin. The present study was undertaken to investigate the role of insulin on the early phase of allergic airway inflammation.

Methods

Diabetic male Wistar rats (alloxan, 42 mg/Kg, i.v., 10 days) and controls were sensitized by s.c. injection of ovalbumin (OA) in aluminium hydroxide 14 days before OA (1 mg/0.4 mL) or saline intratracheal challenge. The following analyses were performed 6 hours thereafter: a) quantification of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant (CINC)-1 in the bronchoalveolar lavage fluid (BALF) by Enzyme-Linked Immunosorbent Assay, b) expression of E- and P- selectins on lung vessels by immunohistochemistry, and c) inflammatory cell infiltration into the airways and lung parenchyma. NPH insulin (4 IU, s.c.) was given i.v. 2 hours before antigen challenge.

Results

Diabetic rats exhibited significant reduction in the BALF concentrations of IL-1β (30%) and TNF-α (45%), and in the lung expression of P-selectin (30%) compared to non-diabetic animals. This was accompanied by reduced number of neutrophils into the airways and around bronchi and blood vessels. There were no differences in the CINC-1 levels in BALF, and E-selectin expression. Treatment of diabetic rats with NPH insulin, 2 hours before antigen challenge, restored the reduced levels of IL-1β, TNF-α and P-selectin, and neutrophil migration.

Conclusion

Data presented suggest that insulin modulates the production/release of TNF-α and IL-1β, the expression of P- and E-selectin, and the associated neutrophil migration into the lungs during the early phase of the allergic inflammatory reaction.