title: Effect Of α2-Adrenergic Agonists And Antagonists On Cytokine Release From Human Lung Macrophages Cultured In Vitro.
abstract: The most trusted hypothesis to explain how α2-adrenergic agonists may preserve pulmonary functions in critically ill patients is that they directly act on macrophages by interfering with an autocrine/paracrine adrenergic system that controls cytokine release through locally synthetized noradrenaline and α1- and α2-adrenoreceptors. We tested this hypothesis in primary cultures of resident macrophages from human lung (HLMs). HLMs were isolated by centrifugation on percoll gradients from macroscopically healthy human lung tissue obtained from four different patients at the time of lung resection for cancer. HLMs from these patients showed a significant expression of α2A, α2B and α2C adrenoreceptors both at the mRNA and at the protein level. To evaluate whether α2 adrenoreceptors controlled cytokine release from HMLs, we measured IL-6, IL-8 and TNF-α concentrations in the culture medium in basal conditions and after preincubation with several α2-adrenergic agonists or antagonists. Neither the pretreatment with the α2-adrenergic agonists clonidine, medetomidine or dexdemetomidine or with the α2-adrenergic antagonist yohimbine caused significant changes in the response of any of these cytokines to LPS. These results show that, different from what reported in rodents, clonidine and dexdemetomidine do not directly suppress cytokine release from human pulmonary macrophages. This suggests that alternative mechanisms such as effects on immune cells activation or the modulation of autonomic neurotransmission could be responsible for the beneficial effects of these drugs on lung function in critical patients.
authors.affiliation: Università di Salerno, Department of Medicine and Surgery, Via Allende, 84081 Baronissi, (SA) Italy.
authors.forename: O
authors.initials: O
authors.lastname: Piazza
authors.affiliation: Università degli Studi di Napoli Federico II, Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), Naples, Italy.
authors.forename: R I
authors.initials: RI
authors.lastname: Staiano
authors.affiliation: Università degli Studi di Napoli Federico II, Department of Neurosciences, Naples, Italy; Federico II University Hospital, Naples, Italy.
authors.forename: E
authors.initials: E
authors.lastname: De Robertis
authors.affiliation: Università Cattolica del Sacro Cuore, Anaesthesiology and Intensive Care, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Conti
authors.affiliation: Università di Salerno, Department of Medicine and Surgery, Via Allende, 84081 Baronissi, (SA) Italy.
authors.forename: V
authors.initials: V
authors.lastname: Di Crescenzo
authors.affiliation: Università degli Studi di Napoli Federico II, Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Loffredo
authors.affiliation: Università degli Studi di Napoli Federico II, Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Marone
authors.affiliation: Università di Salerno, Department of Medicine and Surgery, Via Allende, 84081 Baronissi, (SA) Italy.
authors.forename: G Zito
authors.initials: GZ
authors.lastname: Marinosci
authors.affiliation: Università degli Studi di Napoli Federico II, Department of Neurosciences, Naples, Italy; Federico II University Hospital, Naples, Italy.
authors.forename: M M
authors.initials: MM
authors.lastname: Cataldi
keywords: clonidine; cytokines; dexmedetomidine; macrophages; medetomidine; yohimbine