Methylprednisolone differentially regulates IL-10 and tumour necrosis factor (TNF) production during murine endotoxaemia

Abstract

SUMMARYIL-10 is an endogenous antiinflammatory cytokine that inhibits TNF biosynthesis and protects mice from lipopolysaccharide (LPS)-induced lethality. As synthetic glucocorticoids are widely used as antiinflammatory agents, we analysed the effects of methylprednisolone administration on IL-10 biosynthesis during murine endotoxaemia. We found that low doses of methylprednisolone (2-10 mg/ kg) markedly inhibited TNF production but did not affect serum levels of IL-10, while a high methylprednisolone dose (50 mg/kg) increased LPS-induced IL-10 levels. In parallel, we observed that LPS-induced IL-10 production is TNF-independent in this experimental setting. Experiments conducted in vitro indicated that methylprednisolone (from 0 . 01 to 100

Improved survival ratios correlate with myeloid dendritic cell restoration in acute-on-chronic liver failure patients receiving methylprednisolone therapy

“…However, this therapy has not been shown to have a satisfactory clinical effect and has not been established definitively. 12,13 As such, we speculate that finding immune markers as a surrogate for therapeutic efficacy would define the beneficial effects of this therapy. The decrease in DC numbers in peripheral blood may be an important phenomenon of ACLF pathogenesis.…”

“…The altered hepatic microenvironment or improved liver function or the recruitment of Notably, the present study was conducted on HBV-associated ACLF patients relative to acute hepatic failure. 12,13,22 In addition, the control and treatment groups were homogeneous in the etiology of liver disease (all patients had chronic HBV infection related liver disease) and were comparable in terms of their baseline clinical characteristics (Table 1). Therefore, this design, at least to some extent, provides more convincing data related to the efficacy of MP in the treatment of ACLF patients.…”

“…Clinical findings and experimental rodent models suggest that corticosteroids can suppress the effects of these activated inflammatory cells. 12,13 However, only some of the HBV-ACLF patients treated with corticosteroids were cured without liver transplantation. As such, the identification of immune parameters as indicators for the efficacy of corticosteroid treatment is urgently needed.…”

Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro

“…Once this receptor is activated it translocates into the nucleus where it interacts with specific transcription factors (AP-1 and NF-кB) and prevents the transcription of pro-inflammatory genes. GCs inhibit the production of inflammatory cytokines, including TNF-α and IL-10, by LPS activated monocytes/macrophages and protect animals from LPS-induced lethality (Beutler et al 1986;Fantuzzi et al 1994;Gonzalez et al 1993;Marchant et al 1996). Endogenous GCs are produced during the course of inflammatory responses, including endotoxic shock (Marchant et al 1996).…”

Anti-inflammatory functions of glucocorticoid-induced genes

“…In these complex clinical settings the cellular source of IL-10 is often unclear. In vitro, purified monocytes or macrophages but not B or T cells expressed IL-10 in response to GC (Ehrchen et al, 2007;Hodge et al, 1999;Marchant et al, 1996;Mozo et al, 2004). Differentiation of dendritic cells (dc) in the presence of GC gave rise to a dc population with decreased cell surface costimulatory molecule expression and increased capacity to express IL-10 when stimulated (de Jong et al, 1999;Dong et al, 2003;Duperrier et al, 2005;Matyszak et al, 2000;Piemonti et al, 1999;Rea et al, 2000;Rozkova et al, 2006).…”