Inflammatory response induced by Helicobacter pylori infection in lung.

Helicobacter pylori is a microorganism that in the last years has been associated with extragastric disorders such as respiratory diseases, however, its impact on lung is partially understood. The aim of this work was to study infection impact of H. pylori on the inflammatory markers expression at the pulmonary level using an animal model. Infection was performed by BALB/c wild type (WT) mice orotracheal instillation with 20 µl of 1 × 108H. pylori reference strain suspension once per day throughout 3 days. Inflammatory response was evaluated at 3, 7, 14, 21 and 30 days post infection. Lung was aseptically removed and pulmonary edema index values showed a significant change at 30 days of infection. Hematoxylin-Eosin (H-E) stain allowed to visualizing H. pylori presence in lung samples at 3 days of infection near the phagocytic cells or in the alveoli lumen. Bronchoalveolar lavage (BAL) was used for inflammatory response evaluation. Lactate dehydrogenase values showed a gradual increase in infected animals along infection time. Protein concentrations in mg/ml from BAL increased significantly at 7 days in infected animals. Macrophages viability obtained from BAL, decreased at the first moment of infection, maintaining constant values along contamination time. Results obtained demonstrate an inflammatory response in lung after orotracheal H. pylori infection and suggest that the pathogenic mechanism is strongly evidenced by tissue damage, endothelial dysfunction inflammatory mediators and markers expression at the pulmonary level.

Study of Helicobacter pylori infection on lung using an animal model.

Helicobacter pylori infection has been reported to be associated with extra-digestive disorders such as respiratory diseases; however, the impact of H. pylori on lung is incompletely understood. Inflammatory response is mediated by the release of cytokines, interferon, and enzymes such as metalloproteinases (MMPs). This may contribute to collagen accumulation during the early phase of infection. MMP expression is an important factor for the proliferation and infiltration of lung cells in the process of fibrosis formation. The aim of this work was to study the impact of the infection with H. pylori on lung using a mouse model. We looked for histological lesions of lung infected with the microorganism as well as the expression of inflammatory and of endothelial dysfunction markers. C57BL/6 wild type (WT) mice were infected by orotracheal instillation with 20 µl of 1 × 108H. pylori reference strain suspension once per day for 3 days. Animals infected and controls were sacrificed at 3, 7, 14, 21 and 30 days. The lung from mice were stained with Hematoxylin-Eosin (H-E), Masson's Trichromic and Periodic Acid Schifft (PAS) for histological study. Also, lipid hydroperoxides and enzime catalase (CAT) activity were determined. Expression level of multiple markers implicated in inflammation (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-4, IL-6, IL-8, IL-10; metalloproteinase MMP-9) and markers of endothelial dysfunction (I-CAM and V-CAM) was determined from lung tissues mRNA using RT-PCR. Results showed that H. pylori induced morphological changes in the lung tissue with recruitment of inflammatory cells and lung parenchymal cell degradation. The mRNA of IL-1ß and TNF-α; MMP-9, I-CAM and V-CAM increased at 3-7 days infections. Also, iNOS, IL-8 and Phosphocholine cytidyltransferase (CCT) increased with lung injury. Anti-inflammatory interleukin as: IL-4, and IL-10 increased at 7 and 14 days post infection respectively. The results obtained suggest that the pathogenic mechanism of H. pylori on lung could be strongly associated with lung injury as indicate the expression increased of inflammatory mediators and markers of endothelial dysfunction.