Substance P in Long-Lasting Asthma: Immunoinflammatory pathways

Todo-Bom, A; Mota-Pinto, A; Vale-Pereira, S; Alves, V; Dourado, M; Santos-Rosa, M

http://hdl.handle.net/10400.4/780

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Background: Substance P (SP) was described at the beginning of the 20th Century, and its biological action was recognized to have implications in neurogenic inflammation and constriction of smooth muscles. The changes associated with inflammatory chronicity can compromise organ function reversibility. The role of neuromechanisms in the pathology of the disease has been investigated in order to achieve better diagnosis and therapeutic approaches. The stimulation of human cells, such as macrophages and polymorphonuclear cells by SP leads to their activation and to the release of reactive oxygen species (ROS) by these cells. Consequently, a continuous inflammatory disability is observed, mainly if a decrease in antioxidant defence occurs. SP is a substrate for dipeptidyl peptidase IV (DPPIV), which is a multifunctional molecule with enzymatic and proinflammatory activities. CD26 is considered an activation T cell marker. The aim of the present study was to analyse if serum SP values in long-lasting asthma patients were related to lung function parameters. It was also decided to analyze the relationship of SP with superoxide dismutase (SOD) and total antioxidant activity in serum (TAS), as well as its association to CD26/DPPIV values considering their immunological and inflammatory properties. Methods/Data base: A group of individuals older than 65 years, including 64 asthmatic patients (mean age 72±5 years) and 41 healthy individuals (mean age 79±7years) was selected. Both subgroups were submitted to clinical observation, to skin prick tests (SPT) and to SP, TAS, SOD, and DPPIV determinations. T cell CD26 typing was also performed. Lung function tests were done on all patients. Results: Among the patients studied, 42 had positive skin tests, mainly to house dust mites. Asthmatic patients showed a significant increase in SP values (116.2±138.9 vs 39.5±17.9 pg/ml) when compared to controls and a significant decrease in TAS levels (.85±.13 vs .91±.10 mM) and in SOD levels (588.1±156.l vs 822.9±179.5 U/gHb). All patients were clinically stable and presented an average percentage of predict forced expiratory volume in the first second (FEV1) of 73.6±25.3 and median expiratory flow percentage of predict (MEF50) of 38.8±26.7. DPPIV values were significantly increased in asthmatics compared to controls (69.7±15.2 vs 58.6±14.3 U/L). The CD26 expression was only slightly increased in asthmatic patients (41.9±10.2 vs 39.4±11.4). Conclusion: These results confirm the role of SP in asthma and give a contribution for a better knowledge of the immunoinflammatory pathway associated with this chronic disorder. A final goal for these studies would be to achieve a better therapeutic approach in order to improve the outcome of asthmatic patients.