title: The combination of endotoxin and dexamethasone induces type II interleukin 1 receptor (IL-1r II) in monocytes: a comparison to interleukin 1 beta (IL-1 beta) and interleukin 1 receptor antagonist (IL-1ra).
abstract: Soluble type II interleukin 1 receptor (IL-1r II) and interleukin 1 receptor antagonist (IL-1ra) regulate inflammation by competitively inhibiting the binding of IL-1 beta to the signalling IL-1 receptor. In addition, glucocorticoids also regulate IL-1 beta by suppressing gene transcription. More recently, glucocorticoids have been shown to increase soluble IL-1r II concentrations, which may contribute to their anti-inflammatory properties. Interestingly, increased serum levels of soluble IL-1r II and IL-1ra have been measured in septic patients, although the mechanism is unclear. In this respect, the authors characterize new pathways in which IL-1r II and IL-1ra may be regulated in sepsis through combined stimulation with lipopolysaccharide (LPS) and dexamethasone of peripheral blood mononuclear cells (PBMC). This paper confirms that while dexamethasone induces release of IL-1r II, LPS augments dexamethasone-induced IL-1r II release 45-fold. Furthermore, LPS plus dexamethasone induces IL-1r II protein and mRNA, whereas LPS alone does not. Additionally, it was shown by flow cytometric analysis that the monocyte is the primary IL-1r II producer in response to LPS and dexamethasone administration. Therefore, LPS and dexamethasone synergism in IL-1r II induction may be important in controlling IL-1 beta effects. In contrast, LPS alone induces IL-1ra, while dexamethasone attenuates this LPS-induced response. Although IL-1r II and IL-1ra may work together to suppress IL-1 beta effects in sepsis, inflammatory cells differentially regulate these cytokines.
authors.affiliation: Department of Internal Medicine, Ohio State University, Columbus 43210, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Brown
authors.forename: H A
authors.initials: HA
authors.lastname: Dare
authors.forename: C B
authors.initials: CB
authors.lastname: Marsh
authors.forename: M D
authors.initials: MD
authors.lastname: Wewers
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D053574:Receptors, Interleukin-1 Type II; D012795:Sialoglycoproteins / Q000096:biosynthesis*
chemical_list: D005938:Glucocorticoids; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D012795:Sialoglycoproteins; D003907:Dexamethasone