title: Oral administration of lactoferrin inhibits inflammation and nociception in rat adjuvant-induced arthritis.
abstract: Lactoferrin (LF) is a ubiquitous protein which exists in milk, plasma, synovial fluids, cerebrospinal fluid and other biological fluids. LF is also well known as a natural immunomodulator. Recently, we found that bovine milk-derived LF (BLF) produced micro-opioid receptor-mediated analgesia. In this study, we examined whether oral administration of BLF causes anti-nociceptive and anti-inflammatory effects, and also whether it modulates LPS-induced TNF-alpha and IL-10 production in rat model of rheumatoid arthritis (RA), rat adjuvant arthritis. BLF was administrated once daily, starting 3 hr before (preventive experiment) or 19 days after (therapeutic experiment) adjuvant injection. In both experiments, BLF suppressed the development of arthritis and the hyperalgesia in the adjuvant-injected paw. The single-administered BLF produced a dose-dependent analgesia, which was reversed by naloxone, in the adjuvant arthritis rats. Both repeated and single administration of BLF suppressed TNF-alpha production and increased IL-10 production in the LPS-stimulated adjuvant arthritis rats. These results suggest that orally administered BLF has both preventive and therapeutic effects on the development of adjuvant-induced inflammation and pain. Moreover, the immunomodulatory properties of BLF, such as down-regulation of TNF-alpha and up-regulation of IL-10, could be beneficial in the treatment of RA. Thus, we concluded that LF can be safely used as a natural drug for RA patients suffering from joint pain.
authors.affiliation: Department of Veterinary Physiology, Faculty of Agriculture, Tottori University, Japan.
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Hayashida
authors.forename: Toshiro
authors.initials: T
authors.lastname: Kaneko
authors.forename: Takashi
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Shimizu
authors.forename: Kunio
authors.initials: K
authors.lastname: Ando
authors.forename: Etsumori
authors.initials: E
authors.lastname: Harada
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy*; D016753:Interleukin-10 / Q000096:biosynthesis; D007781:Lactoferrin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009270:Naloxone; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009270:Naloxone; D007781:Lactoferrin