PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 9632909

Lung inflammatory response in pneumonia.

C Montón·A Torres
View original source ↗Export metadata ↓

Abstract

In normal conditions, alveolar macrophages (AMs) are the main cells that respond to bacteria that reach lower airways. However, if the microbial inoculum is too high or too virulent to be stopped by AM alone, these cells recruit polymorphonuclear neutrophils (PMN) into the alveoli from the vascular compartment. Cytokines, such as tumour necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-beta), interleukin-6 (IL-6), and interleukin-8 (IL-8), secreted by the AM are able to attract PMN enhanced for phagocytosis, ready to destroy the invading pathogens. However, excessive cytokine production has deleterious effects, with a systemic inflammatory response (sepsis) that can lead to multiorganic failure and death. Other cytokines, such as interleukin-10 (IL-10) balance this response, attenuating several inflammatory mechanisms. The inflammatory lung response in pneumonia has been well studied in animals, and more recently in humans, using bronchoalveolar lavage to measure some inflammatory mediators (TNF-alpha, IL-1 beta, IL-6, IL-8). From these studies, it seems that: 1) the inflammatory response to pneumonia is compartmentalized for most cytokines (in contrast to adult respiratory distress syndrome (ARDS)), except for IL-6 which is a general marker of inflammation. On the other hand, C-reactive-protein is an acute-phase protein synthesized by the liver through the stimulus of IL-6 that may also be an easy-to-measure marker of inflammation that is directly related to IL-6; 2) some of these cytokines may be useful as prognostic indices; 3) there is no clear relationship between the local lung bacterial burden and the intensity of the inflammatory response; and 4) the administration of granulocyte colony-stimulating factor (G-CSF) is a promising therapeutic approach that is still under clinical investigation. In the future, it is probable that the therapeutic goal in severe pneumonia will be to find the exact point at which inflammation is beneficial but not deleterious. The measurement of the inflammatory response may serve for this purpose.

Explore related subjects

Bronchoalveolar Lavage FluidCytokinesHumansLungMacrophages, AlveolarPneumonia, BacterialRespiratory Distress SyndromeJournal ArticleResearch Support, Non-U.S. Gov'tReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

C Montón, A Torres. 1998. Lung inflammatory response in pneumonia.. https://pubmed.ncbi.nlm.nih.gov/9632909/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2006

Impaired neutrophil chemotaxis in chronic obstructive pulmonary disease.

RATIONALE: Neutrophilic airway inflammation is considered to be a major factor in the pathogenesis of chronic obstructive pulmonary disease (COPD), with sputum and bronchoalveolar lavage neutrophil counts broadly correlating with disease severity. The mechanisms responsible for neutrophil accumulation are poorly understood, but they could involve increased influx and/or survival of these cells. OBJECTIVES: To investigate whether neutrophil chemotactic responsiveness and/or chemotactic activity in airway secretions are increased in subjects with COPD. METHODS: Chemotaxis experiments were performed using induced sputum supernatants from subjects with and without COPD as a source of chemotactic activity, and neutrophils from healthy donors as responder cells. In addition, chemotactic responses to N-formyl-Met-Leu-Phe (fMLP) and interleukin-8 (IL-8/CXCL8) were studied using neutrophils from healthy subjects and subjects with COPD. MEASUREMENTS AND MAIN RESULTS: As reported in the literature, sputum neutrophil counts were significantly increased in subjects with COPD compared with healthy subjects. However, this was associated with reduced chemotactic activity in sputum in COPD, as judged by reduced chemotaxis to the fluid phase of sputum from subjects with COPD compared with healthy subjects. Furthermore, whereas neutrophils from subjects with stage I COPD had normal responses to fMLP and IL-8, subjects with more severe stage II-IV COPD showed reduced levels of spontaneous migration and chemotaxis to fMLP and IL-8. CONCLUSIONS: Neither increased chemotactic activity in the airways nor increased chemotactic responsiveness of neutrophils explains the increased number of these cells in subjects with stable COPD. The implications of the observed reduction in neutrophil chemotactic activity remain to be established.

Bronchoalveolar Lavage Fluid↗
PubMed2006

Synergistically upregulated interleukin-10 production in cocultures of monocytes and T cells after stimulation with respiratory syncytial virus.

BACKGROUND: Respiratory syncytial virus (RSV) is known as a causal factor of severe bronchiolitis in young children. It has also been detected in patients with chronic obstructive pulmonary disease (COPD), a disease that is associated with an increased number of T cells in the bronchial mucosa. Here, we investigated the potential direct interaction between RSV and T cells and its impact on cytokine response. METHODS: Purified human peripheral blood T cells were stimulated with RSV in vitro and analyzed by flow cytometry and fluorescence microscopy. Cytokine expression and release were measured in T cell cultures and in cocultures with peripheral blood monocytes as well as with alveolar macrophages from bronchoalveolar lavage fluid by quantitative real-time PCR and ELISA. RESULTS: It was shown that RSV adhered to the surface of T cells. Stimulation of purified T cells with RSV led to a significant increase in interleukin (IL)-10 mRNA expression after 24 h. Moreover, in cocultures of T cells with monocytes or alveolar macrophages, IL-10 production was synergistically upregulated 24 h after stimulation with RSV. CONCLUSION: These results suggest that RSV can cause an excessive IL-10 response leading to downregulation of antiviral defense mechanisms and reduced elimination of respiratory pathogens when antigen-presenting cells and T cells are simultaneously present on the site of infection. This effect may possibly contribute to high frequencies of respiratory pathogens found in patients with chronic inflammatory airway diseases associated with increased local T cell influx such as COPD.

Bronchoalveolar Lavage Fluid↗