• Tuberculosis and Respiratory Diseases
• /
• v.45 no.6
• /
• pp.1236-1251
• /
• 1998

Background : TNF-$\alpha$ appears to be a central mediator of the host response to sepsis. While TNF-$\alpha$ is mainly considered a proinflammatory cytokine, it can also act as a direct cytotoxic cytokine. However, there are not so many studies about the relationship bet ween TNF-$\alpha$ level and lung injury severity in ALI, particularly regarding the case of ALI caused by direct lung injury such as diffuse pulmonary infection. Recently, a natural defense mechanism, known as the stress response or the heat shock response, has been reported in cellular or tissue injury reaction. There are a number of reports examining the protective role of pre-induced heat stress proteins on subsequent LPS-induced TNF-$\alpha$ release from monocyte or macrophage and also on subsequent LPS-induced ALI in animals. However it is not well established whether the stress protein synthesis such as HSP can be induced from rat alveolar macrophages by in vitro or in vivo LPS stimulation. Methods : We measured the level of TNF-$\alpha$, the percentage of inflammatory cells in bronchoalveolar lavage fluid, protein synthesis in alveolar macrophages isolated from rats at 1, 2, 3, 4, 6, 12, and 24 hours after intratracheal LPS instillation. We performed histologic examination and also obtained histologic lung injury index score in lungs from other rats at 1, 2, 3, 4, 6, 12, 24 h after intratracheal LPS instillation. Isolated non-stimulated macrophages were incubated for 2 h with different concentration of LPS (0, 1, 10, 100 ng/ml, 1, or 10 ${\mu}g/ml$). Other non-stimulated macrophages were exposed at $43^{\circ}C$ for 15 min, then returned to at $37^{\circ}C$ in 5% CO2-95% for 1 hour, and then incubated for 2 h with LPS (0, 1, 10, 100ng/ml, 1, or 10 ${\mu}g/ml$). Results : TNF-$\alpha$ levels began to increase significantly at 1 h, reached a peak at 3 h (P<0.0001), began to decrease at 6 h, and returned to control level at 12 h after LPS instillation. The percentage of inflammatory cells (neutrophils and alveolar macrophages) began to change significantly at 2 h, reached a peak at 6 h, began to recover but still showed significant change at 12 h, and showed insignificant change at 24 h after LPS instillation compared with the normal control. After LPS instillation, the score of histologic lung injury index reached a maximum value at 6 h and remained steady for 24 hours. 35 kDa protein band was newly synthesized in alveolar macrophage from 1 hour on for 24 hours after LPS instillation. Inducible heat stress protein 72 was not found in any alveolar macrophages obtained from rats after LPS instillation. TNF-$\alpha$ levels in supernatants of LPS-stimulated macro phages were significantly higher than those of non-stimulated macrophages(p<0.05). Following LPS stimulation, TNF-$\alpha$ levels in supernatants were significantly lower after heat treatment than in those without heat treatment (p<0.05). The inducible heat stress protein 72 was not found at any concentrations of LPS stimulation. Whereas the 35 kDa protein band was exclusively found at dose of LPS of 10 ${\mu}g/ml$. Conclusion : TNF-$\alpha$ has a direct or indirect close relationship with lung injury severity in acute lung injury or acute respiratory distress syndrome. In vivo and in vitro LPS stimulation dose not induce heat stress protein 72 in alveolar macrophages. It is likely that 35 kDa protein, synthesized by alveolar macrophage after LPS instillation, does not have a defense role in acute lung injury.

• Tuberculosis and Respiratory Diseases
• /
• v.40 no.6
• /
• pp.631-637
• /
• 1993

Background: In normal adults, ventilation is uneven and greater in the base than the apex of the lung in tidal volume breathing. However infants have fragile chest wall and reduced elastic recoil, resulting in easy closure of peripheral airways especially in the dependent portion of the lung. So ventilation in infants is greater in the apex than the base of the lung. We assumed that in adults whose closing volume is increased, dependent portion could be easily collapsed during tidal breathing and ventilation could be greater in the uppear than than the lower portion of the lung. Methods: We measured spirometry and closing volume(CV) in normal controls and in patients with chronic lung disease. Also we measured fractional distribution of ventilation at supine, left lateral and right lateral decubitus with $^{133}Xe$ ventilation scan in normal controls, patients with normal closing volume and patients with increased closing volume. Results: The subjects consisted of 7 normal controls(mean $age{\pm}SD$, $62.9{\pm}6.1$ years). 6 patients with normal CV($62.8{\pm}8.2$ years) and 7 patients with increased CV($63.0{\pm}15.3$ years). 1) Normal controls have mean(${\pm}SD$) FVC $104{\pm}11%$ of predicted value, $FEV_1\;120{\pm}16%,\;FEV_1/FVC\;112{\pm}5%$ and CV $86.9{\pm}12.5%$. Patients with normal CV have FVC $62{\pm}11%,\;FEV_1\;54{\pm}17%,\;FEV_1/FVC\;84{\pm}23%$ and CV $92.6{\pm}15.5%$. Patients with increased CV, have FVC $53{\pm}9%,\;FEV_1\;38{\pm}13,\;FEV_1/FVC\;69{\pm}16%$ and CV $176.1{\pm}36.6%$, CV was significantly different between two patient groups(p<0.02) 2). In normal controls mean fractional ventilation to left lung was $48.1{\pm}5.3%$ at supine, $54.1{\pm}9.8%$ at dependent and $40.9{\pm}6.5%$ at left uppermost position. In patients with normal CV mean fractional ventilation to left lung was $44.6{\pm}2.1%$ at supine, $59.7{\pm}5.6%$ at left dependent and $31.7{\pm}8.3%$ at left uppermost position. In patients with increased CV mean fractional ventilation to left lung was $48.7{\pm}4.5%$ at supine, $41.7{\pm}6.6%$ at left dependent and $60.9{\pm}15.7%$ at left uppermost position. In normal controls and patients with normal CV, ventilation to left lung at left dependent position tends to be higher than that at supine position but without statisitical significance and it was significantly lower at left uppermost than at left lung dependent position. In patients with increased CV, ventilation to left at left dependent position tends to be higher than that at supine position but without significance and it was significantly higher at left uppermost than that at left dependent position. Conclusion: These data suggest that in patients with increased CV ventilation to one side of lung could be higher at uppermost than at dependent position on lateral decubitus during tidal breathing and this fact should be taken into account in positioning of patients with unilateral lung disease.