期刊
WORLD JOURNAL OF HEPATOLOGY
卷 8, 期 17, 页码 726-730出版社
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.4254/wjh.v8.i17.726
关键词
Acute phase response; Dexamethasone; Endotoxin; Hemoglobin scavenger receptor CD163; Cytokines; Inflammation; Rats
资金
- NOVO Nordisk foundation
- Aarhus University Research Foundation
- Clinical Institute, Aarhus University, Denmark
- Novo Nordisk Fonden [NNF14OC0011537, NNF10OC1013267, NNF14OC0012141] Funding Source: researchfish
AIM: To study the effect of a new anti-CD163-dexamethasone conjugate targeting activated macrophages on the hepatic acute phase response in rats. METHODS: Wistar rats were injected intravenous with either the CD163 targeted dexamethasone-conjugate (0.02 mg/kg) or free dexamethasone (0.02 or 1 mg/kg) 24 h prior to lipopolysaccharide (LPS) (2.5 mg/kg intraperitoneal). We measured plasma concentrations of tumour necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) 2 h post-LPS and liver mRNAs and serum concentrations of the rat acute phase protein alpha-2-macroglobulin (alpha-2-M) 24 h after LPS. Also, plasma concentrations of alanine aminotransferase and bilirubin were measured at termination of the study. Spleen weight served as an indicator of systemic steroid effects. RESULTS: The conjugate halved the alpha-2-M liver mRNA (3.3 +/- 0.6 vs 6.8 +/- 1.1, P < 0.01) and serum protein (201 +/- 48 mu g/mL vs 389 +/- 67 mu g/mL, P = 0.04) after LPS compared to low dose dexamethasone treated animals, while none of the free dexamethasone doses had an effect on liver mRNA or serum levels of alpha-2-M. Also, the conjugate reduced TNF-alpha (7208 +/- 1977 pg/mL vs 21583 +/- 7117 pg/mL, P = 0.03) and IL-6 (15685 +/- 3779 pg/mL vs 25715 +/- 4036 pg/mL, P = 0.03) compared to the low dose dexamethasone. The high dose dexamethasone dose decreased the spleen weight (421 +/- 11 mg vs 465 +/- 12 mg, P < 0.05) compared to controls, an effect not seen in any other group. CONCLUSION: Low-dose anti-CD163-dexamethasone conjugate effectively decreased the hepatic acute phase response to LPS. This indicates an anti-inflammatory potential of the conjugate in vivo.
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