Low-tidal-volume Mechanical Ventilation Induces a Toll-like Receptor 4–dependent Inflammatory Response in Healthy Mice
| Autor: | Leo M. A. Heunks, Gert Jan Scheffer, Jan van Egmond, F. J. J. Halbertsma, Leo A. B. Joosten, Michiel Vaneker, Johannes G. van der Hoeven, Mihai G. Netea, Dirk G. Snijdelaar |
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| Přispěvatelé: | Intensive care medicine, ACS - Pulmonary hypertension & thrombosis |
| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Chemokine Cell Count Lung injury Ligands Auto-immunity transplantation and immunotherapy [N4i 4] Proinflammatory cytokine Invasive mycoses and compromised host [N4i 2] Mice Reference Values Internal medicine Leukocytes Tidal Volume Perception and Action [DCN 1] Animals Medicine RNA Messenger Lung Cells Cultured Inflammation Mice Knockout Chronic inflammation and autoimmunity [UMCN 4.2] medicine.diagnostic_test biology Tumor Necrosis Factor-alpha business.industry Interleukins Interleukin Respiration Artificial Toll-Like Receptor 2 Mice Inbred C57BL Toll-Like Receptor 4 Pathogenesis and modulation of inflammation [N4i 1] TLR2 Anesthesiology and Pain Medicine Endocrinology Bronchoalveolar lavage Immunology biology.protein TLR4 Cytokines Tumor necrosis factor alpha Microbial pathogenesis and host defense [UMCN 4.1] Chemokines business Bronchoalveolar Lavage Fluid Infection and autoimmunity [NCMLS 1] Immunity infection and tissue repair [NCMLS 1] |
| Zdroj: | Anesthesiology, 109(3), 465-472. Lippincott Williams and Wilkins Anesthesiology, 109, 3, pp. 465-72 Anesthesiology, 109, 465-72 Vaneker, M, Joosten, L A, Heunks, L M A, Snijdelaar, D G, Halbertsma, F J, Van Egmond, J, Netea, M G, Van Der Hoeven, J G & Scheffer, G J 2008, ' Low-tidal-volume mechanical ventilation induces a toll-like receptor 4-dependent inflammatory response in healthy mice ', Anesthesiology, vol. 109, no. 3, pp. 465-472 . https://doi.org/10.1097/ALN.0b013e318182aef1 |
| ISSN: | 0003-3022 |
| DOI: | 10.1097/aln.0b013e318182aef1 |
| Popis: | Background Mechanical ventilation (MV) can induce ventilator-induced lung injury. A role for proinflammatory pathways has been proposed. The current studies analyzed the roles of Toll-like receptor (TLR) 4 and TLR2 involvement in the inflammatory response after MV in the healthy lung. Methods Wild-type (WT) C57BL6, TLR4 knockout (KO), and TLR2 KO mice were mechanically ventilated for 4 h. Bronchoalveolar lavage fluid was analyzed for presence of endogenous ligands. Lung homogenates were used to investigate changes in TLR4 and TLR2 expression. Cytokines were measured in lung homogenate and plasma, and leukocytes were counted in lung tissue. Results MV significantly increased endogenous ligands for TLR4 in bronchoalveolar lavage fluid and relative messenger RNA expression of TLR4 and TLR2 in lung tissue. In lung homogenates, MV in WT mice increased levels of keratinocyte-derived chemokine, interleukin (IL)-1alpha, and IL-1beta. In TLR4 KO mice, MV increased IL-1alpha but not IL-1beta, and the increase in keratinocyte-derived chemokine was less pronounced. In plasma, MV in WT mice increased levels of IL-6, keratinocyte-derived chemokine, and tumor necrosis factor alpha. In TLR4 KO mice, MV did not increase levels of IL-6 or tumor necrosis factor alpha, and the response of keratinocyte-derived chemokine was less pronounced. MV in TLR2 KO mice did not result in different cytokine levels compared with WT mice. In WT and TLR2 KO mice, but not in TLR4 KO mice, MV increased the number of pulmonary leukocytes. Conclusions The current study supports a role for TLR4 in the inflammatory reaction after short-term MV in healthy lungs. Increasing the understanding of the innate immune response to MV may lead to future treatment advances in ventilator-induced lung injury, in which TLR4 may serve as a therapeutic target. |
| Databáze: | OpenAIRE |
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