Bovine lactoferrin ingestion protects against inflammation via IL-11 induction in the small intestine of mice with hepatitis.
Accumulating evidence suggests that orally ingested lactoferrin protects against inflammation. To assess the efficacy of orally administered bovine lactoferrin (bLF) against hepatitis and to identify the underlying mechanism, in the present study, we used four mouse models of hepatitis induced by d-galactosamine (GalN), carbon tetrachloride (CCl4), GalN plus lipopolysaccharide (LPS) and zymosan plus LPS. Intraperitoneal (i.p.) injection of GalN (500 mg/kg body weight) in mice treated with bovine serum albumin (BSA) for 14 d significantly increased serum aspartate aminotransferase (AST) concentrations compared with the untreated mice. However, orally administered bLF reduced AST concentrations compared with BSA treatment. In mice that received a single injection (0·4 ml/kg) and twice-weekly injections (0·08 ml/kg) of CCl4 for 24 weeks and pretreated with bLF for 14 d and 24 weeks, respectively, significantly suppressed alanine aminotransferase and AST concentrations were observed compared with the BSA-treated control. Oral administration of bLF for 14 d before i.p. injection of LPS (5 mg/kg) plus GalN (1 g/kg) significantly improved the survival rate. In mice that received intravenous injection of zymosan (25 mg/kg) and LPS (15 μg/kg) at 7 d intervals, bLF reduced the elevation of AST concentrations and enhanced the production of IL-11 and bone morphogenetic protein 2 in the small intestine compared with the BSA-treated control. To evaluate the effects of IL-11, we used IL-11 receptor α-null mice treated with GalN, CCl4 and zymosan plus LPS. In this group, the activity of bLF was not significantly different from that of BSA. These data indicate that orally ingested bLF enhances the expression of IL-11 in the small intestine and up-regulates protective activity in mice with hepatitis.
Food Science and Technology Institute, Morinaga Milk Industry Company Limited, 5-1-83 Higashihara, Zama, Kanagawa 228-8583, Japan.
Tetsuya
T
Kuhara
Food Science and Technology Institute, Morinaga Milk Industry Company Limited, 5-1-83 Higashihara, Zama, Kanagawa 228-8583, Japan.
Azusa
A
Tanaka
Food Science and Technology Institute, Morinaga Milk Industry Company Limited, 5-1-83 Higashihara, Zama, Kanagawa 228-8583, Japan.
Koji
K
Yamauchi
Food Science and Technology Institute, Morinaga Milk Industry Company Limited, 5-1-83 Higashihara, Zama, Kanagawa 228-8583, Japan.
Keiji
K
Iwatsuki
D061605:Administration, Intravenous; D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood*; D000704:Analysis of Variance; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002417:Cattle; D004195:Disease Models, Animal; D006505:Hepatitis / Q000378:metabolism* / Q000473:pathology; D017370:Interleukin-11 / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007781:Lactoferrin / Q000008:administration & dosage* / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger; D012710:Serum Albumin, Bovine / Q000008:administration & dosage* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D055396:Bone Morphogenetic Protein 2; D017370:Interleukin-11; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D012710:Serum Albumin, Bovine; D000410:Alanine Transaminase; D007781:Lactoferrin