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-a(TNF-a) and interleukin 6(IL-6) 2 h post-LPS and liver m RNAs and serum concentrations of the rat acute phase protein a-2-macroglobulin(a-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 a-2-M liver m RNA(3.3 ± 0.6 vs 6.8 ± 1.1, P < 0.01) and serum protein(201 ± 48 μg/mL vs 389 ± 67 μg/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 m RNA or serum levels of a-2-M. Also, the conjugate reduced TNF-a(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. 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 We measured plasma concentrations of tumor necrosis factor-a (TNF-a) and interleukin 6 (IL-6) for 24 h prior to lipopolysaccharide (LPS) (2.5 mg / kg intraperitoneal) post-LPS and liver m RNAs and serum concentrations of the rat acute phase protein a-2-macroglobulin (a-2-M) 24 h after LPS. 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 a-2-M liver m RNA (3.3 ± 0.6 vs 6.8 ± 1.1, P <0.01) and serum protein (201 ± 48 μg / mL vs 389 ± 67 μg / mL, P = 0.04) after LPS compared to low dose dexamethasone treated animals, while none of the fre Also, the conjugate reduced TNF-a (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.