| The Lung Expression of Proinflammatory Cytokines, TNF-alpha and Interleukin 6, in Early Periods of Endotoxemia. |
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Seung Hyug Moon, Yong Hoon Kim, Choon Sik Park, Shin Je Lee |
1Department of Internal Medicine, Soonchunyang University, College of Medicine, Chunan, Korea.
2Department of Microbiology, Soonchunyang University, College of Medicine, Chunan, Korea. |
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| Abstract |
BACKGROUND
The immediate host response to LPS is the production of proinflammatory cytokines that act as intercellular mediators in inflammatory reactions, including acute lung injury. These "early response" cytokines transmit signals from recognition cells to target or effector cells. This host response is futher amplified by the expression of leukocyte chemoattractants, growth factors, and adhesion molecules, resulting in an array of proinflammatory events. This experiment was performed to define the lung origin of proinflammatory cytokines, such as TNF-alpha IL 6 in early periods of endotoxin induced acute lung injury (ALl). METHOD: The healthy male Sprague-Dawley, weighted 150-250g, were divided into saline control (NC) and endotoxemia-induced ALl (ETX-), and leukopenic endotoxemia-induced ALl (CPA-ETX-Group) which was induced by cyclophosphamide, 70 mg/kg i.p. injection. Acute lung injury was evoked by LPS, 5 mg/kg, intravenously administered. Bronchoalveolar lavage was performed at 0, 3, 6 h after LPS-treated to estimate the influx of phagocytes and concentration of total protein, and cytokines as TNF-alpha and IL 6 by a bioassy using MTT method. We also examined the localization of TNF-alpha and IL 6 protein in endotoxemia-challenged lung tissue by immunohistochemical stain (IH). RESULTS: The total cell, macrophage and PMN count in BALF were elavated in ETX group compared to NC (p<0.05). In CPA-ETX group, total cell and macrophage count in BALF were not changed compared to NC, but PMN count was markedly reduced and it took part. in less than 0.1% of total BAL cells (p<0.01). The protein concentration in BALF were significantly increased in ETX and CPA-ETX group compared to NC (p<0.05), but there was signifcant difference between ETX- and CPA-ETX group only at 6 h (p<0.05). This observation suggested that even if PMNs are involved in the pathogenesis of acute lung injury, their role cannot be viewed as essential. The concentration of TNF-alpha and IL 6 in BALF was significantly increased in the ETX- and CPA-ETX group compared to NC. There was no difference between ETX- and CPA-ETX group. In IH, anti-TNF-alpha- and anti-IL 6 antibody was strongly localized at interstitial monocytes and alveolar macro-phages in endotoxemia-challenged lung tissue. From above point of view, activated alveolar macrophage/monocyte considered as a prominent source of proinflammatory cytokines in endotoxemia-challenged lung injury. CONCLUSION: The prominent source of proinflammatory cytokines in early periods of endotoxemia-induced lung injury will be the activated resident macrophages like an alveolar macrophage and interstitial monocytes. The pulmonary macrophage/monocyte will impact the initiation and continuance of lung injury without PMNs s certain inflammatory role, particularly in endotoxemia-induced acute lung injury. |
| Key Words:
Acute lung injury, Proinflammatory cytokines, Alveolar macrophage/monocyte |
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