Interleukin 1β, Tumor Necrosis Factor Alpha, and Interleukin 8 in Bronchoalveolar Lavage Fluid of Patients with Diffuse Panbronchiolitis: A Potential Mechanism of Macrolide Therapy

Respiration ◽  
1996 ◽  
Vol 63 (1) ◽  
pp. 42-48 ◽  
Author(s):  
Osamu Sakito ◽  
Jun-ichi Kadota ◽  
Shigeru Kohno ◽  
Koh Abe ◽  
Ryo Shirai ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Bronchoalveolar Lavage ◽  
Tumor Necrosis ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Potential Mechanism ◽  
Necrosis Factor Alpha ◽  
Diffuse Panbronchiolitis ◽  
Factor Alpha ◽  
Necrosis Factor

Low-tidal-volume Mechanical Ventilation Induces a Toll-like Receptor 4–dependent Inflammatory Response in Healthy Mice

2008 ◽  
Vol 109 (3) ◽  
pp. 465-472 ◽  
Author(s):  
Michiel Vaneker ◽  
Leo A. Joosten ◽  
Leo M. A. Heunks ◽  
Dirk G. Snijdelaar ◽  
Feico J. Halbertsma ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Toll Like Receptor ◽  
Necrosis Factor Alpha ◽  
Ventilator Induced Lung Injury ◽  
Factor Alpha ◽  
Necrosis Factor

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.

Soluble Complement Receptor Type 1 Inhibited the Systemic Organ Injury Caused by Acid Instillation into a Lung

1996 ◽  
Vol 85 (5) ◽  
pp. 1120-1128 ◽  
Author(s):  
Hideo Nishizawa ◽  
Hiroshi Yamada ◽  
Hiroshi Miyazaki ◽  
Maria Ohara ◽  
Kazuhiro Kaneko ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Bronchoalveolar Lavage ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Protein Concentration ◽  
Alpha Activity ◽  
Necrosis Factor Alpha ◽  
Contralateral Lung ◽  
Factor Alpha ◽  
Necrosis Factor

Background Acid aspiration into one lung causes contralateral lung injury and systemic organ injury; this injury is thought to be mediated by the sequestration of activated neutrophils. Recombinant human soluble complement receptor 1 (sCR1) inhibits both the classical and alternative complement pathways; this study investigated the role of the complement system in unilateral acid lung injury by measuring the effects of administering sCR1 before or immediately after acid instillation. Methods Anesthetized rats (n = 18 in each group) underwent tracheostomy and insertion of a cannula into the anterior segment of the left lung. Then either 0.1 ml 0.1 N hydrochloric acid (HCl group) or 0.1 ml pH 7.4 phosphate buffered-saline (PBS group) was instilled. Fifteen minutes before (pre-sCR1 group) or 15 min after (post-sCR1 group) the acid was instilled, 10 mg/kg sCR1 was administered intravenously. Four hours after the acid instillation, rats were killed. In an additional 4 rats in each group, blood and bronchoalveolar lavage fluids obtained 1 h after the instillation of either acid or PBS were analyzed for tumor necrosis factor-alpha activity. Results The instillation of acid led to an increased wet-to-dry ratio of 5.2 +/- 0.1 in the acid-instilled lungs compared with their contralateral lungs (4.7 +/- 0.06). These values were greater than the values of 4.6 +/- 0.2 and 4.5 +/- 0.03 in the PBS-instilled lungs and their contralateral lungs, respectively (P < 0.05). The administration of sCR1 before or immediately after the instillation of acid did not attenuate the increase in the wet-to-dry ratio of the acid-instilled lungs. However, the small but consistent increase in the wet-to-dry ratio of the contralateral lungs was attenuated by the sCR1 infusions (P < 0.05). The instillation of acid increased the protein concentration in the bronchoalveolar lavage fluids from the injured lungs (1,000 +/- 206 micrograms/ml) compared with the protein concentration measured in the bronchoalveolar lavage fluids from their contralateral lungs (254 +/- 55 micrograms/ml). The administration of sCR1 before or immediately after the instillation of acid did not decrease the protein concentration in the bronchoalveolar lavage fluids from the acid-instilled lungs. The myeloperoxidase activity was increased in the acid-instilled lung, in their contralateral lung, and in the small intestines of the animals. The infusions of sCR1 before or immediately after the administration of acid led to significant decreases in the myeloperoxidase activities measured in the lungs and the intestines of the treated animals. Plasma tumor necrosis factor-alpha activity was only increased (2.7 +/- 1.1 U/ml) in the animals that had received acid instillations. The infusions of sCR1, administered either before or immediately after the acid instillations, significantly decreased the measured tumor necrosis factor-alpha activity in the plasma (0.5 +/- 0.6 and 1.0 +/- 0.7 U/ml, respectively). Conclusions The results suggest that the complement system plays an important role in the pathogenesis of the injury of the contralateral lung and of the small intestine after unilateral instillation of acid to the lung. Further investigation is warranted to determine the clinical utility of antiinflammatory agents in acid-induced lung injury.

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