Insulin modulates cytokine release and selectin expression in the early phase of allergic airway inflammation in diabetic rats.
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)-1beta, tumor necrosis factor (TNF)-alpha 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-1beta (30%) and TNF-alpha (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-1beta, TNF-alpha and P-selectin, and neutrophil migration.


CONCLUSIONS
Data presented suggest that insulin modulates the production/release of TNF-alpha and IL-1beta, the expression of P- and E-selectin, and the associated neutrophil migration into the lungs during the early phase of the allergic inflammatory reaction.
Martins
Joilson O
JO
Institute of Heart InCor, LIM-11, University of São Paulo Medical School, Av Dr Arnaldo, São Paulo 01246903, Brazil. martinsj@usp.br
Campos
Carlos A L
CA
Cruz
José W M C
JW
Manzolli
Simone
S
Alves
Venâncio A F
VA
Vianna
Elcio O
EO
Jancar
Sonia
S
Sannomiya
Paulina
P
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D054360:Chemokine CXCL1 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000276:immunology* / Q000494:pharmacology; D007336:Insulin, Isophane / Q000276:immunology* / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D019007:P-Selectin / Q000378:metabolism; D011014:Pneumonia / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
D001786:Blood Glucose; D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D016207:Cytokines; D019040:E-Selectin; D007004:Hypoglycemic Agents; D053583:Interleukin-1beta; D019007:P-Selectin; D014409:Tumor Necrosis Factor-alpha; D007336:Insulin, Isophane; D010047:Ovalbumin