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)
Brown, E.A.; Dare, H.A.; Marsh, C.B.; Wewers, M.D.
Cytokine 8(11): 828-836
ISSN/ISBN: 1043-4666 PMID: 9047079 DOI: 10.1006/cyto.1996.0111
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.