TABLE 1.
Experimental studies of MIF in acute pancreatitis.
| Model | Species | Regimen | Key findings | Refs |
|---|---|---|---|---|
| Cerulein (6 × 50 μg/kg/h; i.p.) | Wistar rats, male | NA | MIF levels were significantly increased in ascitic fluid but not in serum in AP model | Sakai et al. (2003) |
| Cerulein (3 × 20 μg/kg/h; s.c.) + LPS (4 mg/kg; i.v., after last cerulein injection) | Mif −/- and wild type BALB/c mice, male | Anti-PAR-2 Ab (100 μg/animal) or anti-MIF Ab (20 mg/animal), i.v., immediately before first cerulein injection | 1) acute lung injury was less severe in Mif −/− mice of AP complicated by endotoxemia; 2) Anti-MIF Ab or anti-PAR-2 Ab suppressed the AP-induced elevation of lung TLR4 protein expression | Matsuda et al. (2006) |
| CDE diet (for 48 h) | CD-1 mice, female | Anti-MIF Ab (10 mg/kg) or control rabbit IgG, i.p., immediately after the onset of CDE diet, repeated every 12 h | 1) MIF expression was increased in lung of AP model; 2) Anti-MIF Ab improved the survival rate from 16 to 37% in AP mice | Sakai et al. (2003) |
| l-arginine (2 × 2.5 g/kg; i.p., 1 h interval) | Wistar rats | Glucocorticoid agonist (methylprednisolone; 30 mg/kg) or antagonist (RU-38486; 5 mg/kg), s.c., before disease induction | Antagonist treatment led to significantly higher MIF production at 8 and 12 h after AP induction compared with the agonist-treated or non-treated group | Paszt et al. (2008) |
| l-arginine (2 × 5 g/kg; i.p., 1 h interval) | C57BL/6 mice, male | Chlorogenic acid (20 or 40 mg/kg; i.p., 1 h before AP induction) | Chlorogenic acid suppressed AP-induced increase of MIF levels in serum and pancreatic tissue | Ohkawara et al. (2017) |
| l-arginine (2 × 4 g/kg; i.p., 1 h interval) | Mif −/- and WT C57BL/6 mice | ISO-1 (3.5 mg/kg; i.p. 30 min before first l-arginine induction) | 1) pancreatic NF-κB p65, IL-1β, and TNF-α, serum IL-1β and TNF-α levels, and multiple organ injury were significantly reduced in Mif −/- mice with AP; 2) ISO-1 markedly reduced severity of AP in wild type mice | Zhu et al. (2020) |
| TCA (5%, 0.2 ml/min; PD injection) | Wistar rats, male | Anti-MIF Ab (16 mg/kg) or nonspecific rabbit IgG (control) was given 1 h before, immediately after, or 1 h after induction, i.p | 1) MIF levels were increased in serum (peak at 9 h: 197 ± 9 ng/ml), ascitic fluid and lung, but not in pancreas or liver in AP model; 2) Anti-MIF Ab reduced lung TNF-α levels and improved survival rate (88 vs. 44%, given 1 h before; 92 vs. 33%, given immediately; 61 vs. 39%, given 1 h after induction) of AP rats | Sakai et al. (2003) |
| STC (5%, 0.6 ml/kg; PD infusion) | Sprague–Dawley rats, pregnant female | ISO-1 (3.5 mg/kg; i.p., 30 min before STC infusion) | 1) MIF expression in fetal liver was elevated in AP which was reduced by ISO-1 treatment; 2) ISO-1 markedly reduced pancreatic and liver histopathological scores, inhibited activation of myeloperoxidase, NF-κB, IL-1β, TNF-α, and HMGB1 in fetal liver in AP rats | Guo et al. (2018) |
| STC (5%, 1 ml/kg; PD infusion) | Wistar rats, pregnant female | ISO-1 (3.5 mg/kg; i.p., 30 min before STC infusion) | 1) ISO-1 alleviated pathological injury of pancreas and lung, attenuated serum levels of IL-1β, IL-6, and TNF-α, inhibited activation of lung p38 MAPK and NF-κB in AP rats; 2) ISO-1 reduced MIF expression, increased expression of p38 MAPK, p-p38, NF-κB, as well as TNF-α and IL-1β levels of fetal kidney tissue in AP rats | Zhou et al. (2018); Li et al. (2019) |
| STC (5%, 1 ml/kg; PD infusion) | Wistar rats | Ginkgo biloba extract (20 mg/kg; s.c., twice a day pre-operation for 2 days, then given once at the end of the operation) | 1) AP resulted in a significant up-regulation expression of MIF and TNF-α proteins in alveolar macrophage; 2) ginkgo biloba extract down-regulated expression of TNF-α (6 h, p < 0.001; 12 h, p < 0.001) and MIF (6 h, p = 0.095; 12 h, p < 0.001) in alveolar macrophage compared with AP groups | Xu et al. (2014) |
| STC (5%, 1 ml/kg; PD infusion) | Wistar rats, male | NA | The expression of MIF mRNA and protein was significantly upregulated in intrahepatic bile duct cells in AP rats | Wang et al. (2019) |
MIF, macrophage migration inhibitory factor; TCA, taurocholic acid; PD, pancreaticobiliary duct infusion; Ab, antibody; i. p., intraperitoneal; TNF-α, tumor necrosis factor-alpha; NA, not available; CDE, choline deficient ethionine-supplemented; LPS, lipopolysaccharide; i. v., intravenous; PAR-2, protease activated rec eptor-2; TLR, toll-like receptor; s. c., subcutaneous; STC, sodium taurocholate; ISO-1, (S,R)3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester; NF-κB, nuclear factor kappa B; IL, interleukin; HMGB, high mobility group box; MAPK, mitogen-activated protein kinase.