title: Role of tumor necrosis factor-alpha in endotoxin-induced lung parenchymal hyporesponsiveness in mice.
abstract: 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-)1beta, IL-6, and TNF (tumor necrosis factor)alpha in the BALF. Cytokine production was paralleled by 5-HT lung hyporesponsiveness, and intratracheal administration of TNFalpha proved to be very efficient in inhibiting 5-HT responsiveness. In addition, systemic treatment with rolipram, an inhibitor of TNFalpha production, was paralleled by a significant recovery of lung responsiveness. On the contrary, IL-1beta and IL-6 were not demonstrated to play a relevant role in 5-HT hyporesponsiveness. It is concluded that TNFalpha could be a crucial mediator of LPS-induced lung hyporesponsiveness.
authors.affiliation: Department of Preclinical Pharmacology, Dompé S.p.A., Via Campo di Pile, I-67100, L'Aquila, Italy. bertini@dompe.it
authors.forename: L
authors.initials: L
authors.lastname: Brandolini
authors.forename: A
authors.initials: A
authors.lastname: Intilangelo
authors.forename: G
authors.initials: G
authors.lastname: Caselli
authors.forename: R
authors.initials: R
authors.lastname: Bertini
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D007375:Interleukin-1 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D023421:Models, Animal; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha