Role of tumor necrosis factor-alpha in endotoxin-induced lung parenchymal hyporesponsiveness in mice

• Published in: Biochemical pharmacology Vol. 62; no. 8; pp. 1141 - 1144
• Main Authors: Brandolini, Laura, Intilangelo, Assunta, Caselli, Gianfranco, Bertini, Riccardo
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.10.2001; Elsevier Science
• Subjects: 5-hydroxytryptamine; Analysis of Variance; Animals; Biological and medical sciences; Bronchoalveolar Lavage Fluid; Endotoxins - pharmacology; Female; Hyporesponsiveness; Inflammation; Interleukin-1 - physiology; Interleukin-6 - physiology; Lipopolysaccharide; Lipopolysaccharides - pharmacology; Lung - drug effects; Lung - pathology; Lung - physiopathology; Lung parenchyma; Medical sciences; Mice; Models, Animal; Pneumology; Respiratory system : syndromes and miscellaneous diseases; Tumor necrosis factor; Tumor Necrosis Factor-alpha - physiology; Lipopolysaccharide; Hyporesponsiveness; Inflammation; Tumor necrosis factor; 5-hydroxytryptamine; Lung parenchyma; Serotonin; Lung; Cytokine; Rodentia; Parenchyma; Interleukin 1β; Catecholamine; Respiratory system; Endotoxin; Interleukin 6; Toxin; Vertebrata; Mammalia; Mouse; Mechanism of action; Tumor necrosis factor α
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/S0006-2952(01)00757-2

Although changes in airway responsiveness in pulmonary inflammation are commonly related to the action of infiltrated leukocytes, our previous report suggested a direct role of inflammatory cytokines in LPS-induced lung hyporesponsiveness. The aim of this study was to define if cytokines detected in the BALF (bronchoalveolar lavage fluid) of intratracheal LPS-treated mice could be, at least in part, responsible for 5-HT (5-hydroxytryptamine) lung hyporeactivity. Our results show that intratracheal instillation of LPS induced a time-dependent increase in IL-(interleukin-)1β, IL-6, and TNF (tumor necrosis factor)α in the BALF. Cytokine production was paralleled by 5-HT lung hyporesponsiveness, and intratracheal administration of TNFα proved to be very efficient in inhibiting 5-HT responsiveness. In addition, systemic treatment with rolipram, an inhibitor of TNFα production, was paralleled by a significant recovery of lung responsiveness. On the contrary, IL-1β and IL-6 were not demonstrated to play a relevant role in 5-HT hyporesponsiveness. It is concluded that TNFα could be a crucial mediator of LPS-induced lung hyporesponsiveness.