icatibant and Pneumonia

Secretory phospholipases A2 (sPLA2s) induce acute pancreatitis when injected into the common bile duct of rats. Substance P via neurokinin 1 (NK-1) receptors and bradykinin via B2 receptors are described to play important roles in the pathophysiology of acute pancreatitis. This study was undertaken to evaluate the role of substance P and bradykinin in the sPLA2-induced pancreatitis.. Rats were submitted to the common bile duct injection of sPLA2 obtained from Naja mocambique mocambique venom at 300 microg/kg. At 4 hours thereafter, measurement of pancreatic plasma extravasation, pancreatic and lung myeloperoxidase (MPO), serum amylase, and serum tumor necrosis factor alpha levels were evaluated.. Injection of sPLA2 significantly increased all parameters evaluated. Pretreatment with either the NK-1 receptor antagonist SR140333 or the B2 receptor antagonist icatibant largely reduced the increased pancreatic plasma extravasation and circulating levels of tumor necrosis factor alpha. Both treatments partly reduced the MPO levels in the pancreas, whereas in the lungs, icatibant was more efficient to reduce the increased MPO levels. In addition, icatibant largely reduced the serum levels of amylase, whereas SR140333 had no significant effect.. We concluded that NK-1 and B2 receptors can regulate important steps in the local and remote inflammation during acute pancreatitis induced by sPLA2.

Topics: Acute Disease; Amylases; Animals; Bradykinin; Bradykinin B2 Receptor Antagonists; Disease Models, Animal; Lung; Male; Neurokinin-1 Receptor Antagonists; Pancreas; Pancreatitis; Peroxidase; Phospholipases A2, Secretory; Piperidines; Pneumonia; Quinuclidines; Rats; Rats, Wistar; Receptor, Bradykinin B2; Receptors, Neurokinin-1; Substance P; Tumor Necrosis Factor-alpha

The effect of bradykinin (B(1) or B(2)) receptor antagonists was studied in allergic and immune-complex-induced lung inflammation.. Lungs of BALB/c mice were examined 24 h after induction of lung inflammation, either allergic (ovalbumin-sensitized submitted to two aerosol of antigen, one week apart) or immune-complex induced (intratracheal instillation of IgG antibodies followed by intravenous antigen). The bradykinin B(2) receptor antagonist, HOE-140 or bradykinin B(1) receptor antagonist, R-954 were given intraperitoneally (100 microg/kg), 30 min before induction.. In allergic inflammation, pre-treatment with R-954 reduced eosinophil infiltration into the lungs, mucus secretion and the airway hyperreactivity to methacholine. Pre-treatment with HOE-140 increased eosinophil infiltration but did not affect the other parameters. In immune-complex inflammation, HOE-140 increased neutrophil infiltration but not their activation nor the hemorrhagic lesions. R-594 pre-treatment did not change the parameters examined.. These results show important modulatory effects of bradykinin B(1) and B(2) receptor antagonists in both models of lung inflammation.

Topics: Animals; Bradykinin; Bradykinin B1 Receptor Antagonists; Bradykinin B2 Receptor Antagonists; Bradykinin Receptor Antagonists; Bronchoconstriction; Eosinophils; Hypersensitivity; Immune Complex Diseases; Male; Methacholine Chloride; Mice; Mice, Inbred BALB C; Mucus; Ovalbumin; Pneumonia

The effect of bradykinin receptor antagonists was studied in a mouse (C57Bl/6) model of allergic lung inflammation. Bradykinin B(2) receptor antagonist HOE-140 (D-Arg-[Hyp(3),Thi(5),Dtic(7)-Oic(8)]bradykinin) or bradykinin B(1) receptor antagonist R-954 (Ac-Orn[Oic(2),alphaMePhe(5),betaD-Nal(7)Ile(8)]des-Arg(9)-bradykinin) were given i.p. to ovalbumin sensitized mice 30 min before antigen challenge. After 24 h, bronchoalveolar lavage was performed for cell analysis and the lungs were removed for evaluation of airway hyperreactivity and histopathology. Treatment with HOE-140 caused a significant increase in bronchoalveolar lavage cell number: eosinophils (182%), neutrophils (98%), lymphocytes CD(4)(+) (192%), CD(8)(+) (236%), B220 (840%), Tgammadelta(+) (194%) and NK1.1(+) (246%). Hyperreactivity and mucus secretion were not significantly affected in this group. Treatment with R-954 significantly reduced eosinophil (79%) and neutrophil (83%) but has no effect on lymphocytes number in bronchoalveolar lavage fluid. Airway hyperreactivity and mucus secretion were reduced by this treatment (84% and 35%, respectively). These results show important modulatory effect of bradykinin B(1) and B(2) receptors on allergic lung inflammation.

Topics: Animals; Bradykinin; Bradykinin Receptor Antagonists; Bronchoalveolar Lavage Fluid; Male; Mice; Mice, Inbred C57BL; Pneumonia; Receptor, Bradykinin B1; Receptor, Bradykinin B2; Receptors, Bradykinin