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. CONCLUSION: 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.

Allergic airway inflammation inhypothyroid rats

Background: Hormones play a modulating role in allergicinflammation. Hyperthyroidism may increase the severity ofasthma, and hypothyroidism may ameliorate coexistent asthma.The mechanisms regulating this interaction are not completelyunderstood.Objective: The purpose of this study was to test the hypothesisthat thyroid hormones influence the development of allergicairway inflammation after antigen challenge in rats.Methods: The experimental design included either sensitizedor nonsensitized surgically thyroidectomized and sham-operatedrats. Experiments were performed 50 days after surgery.Thyroidectomized rats and sham-operated controls were sensitizedby subcutaneous injection of ovalbumin (OVA) andAl(OH)3 and challenged 14 days later by OVA inhalation.Bronchoalveolar lavages were performed 24 hours after challenge.Results: Compared with controls, thyroidectomized animalspresented markedly decreased cell yields from bronchoalveolarlavage fluid after OVA challenge. The impaired responsewas not related to changes in the number of circulating leukocytes.Determination of antibody serum concentrations indicatedthat thyroidectomized rats presented a marked reductionin the level of anti-OVA IgE compared with controls, withoutsignificant differences in IgG1 and IgG2a serum concentrations.Reversal of the impaired responses was attained by 16-day treatment of hypothyroid animals with thyroxine, but notby 1- or 3-day treatment.Conclusion: The data presented suggest that the continuingdeficiency of thyroid hormones influences the development ofthe inflammatory component of asthma. This is due, at least inpart, to a decrease in the production of IgE. (J Allergy ClinImmunol 1999;104:595-600.).