Bovine glycomacropeptide ameliorates experimental rat ileitis by mechanisms involving downregulation of interleukin 17.
OBJECTIVE
Bovine glycomacropeptide (BGMP) is an inexpensive, non-toxic milk peptide with anti-inflammatory effects in rat experimental colitis but its mechanism of action is unclear. It is also unknown whether BGMP can ameliorate inflammation in proximal regions of the intestine. Our aim was therefore two-fold: first, to determine the anti-inflammatory activity of BGMP in the ileum; second, to characterise its mechanism of action.


METHODS
We used a model of ileitis induced by trinitrobenzenesulphonic acid in rats. Rats were treated orally with BGMP and its efficacy compared with that of oral 5-aminosalicylic acid or vehicle, starting 2 days before ileitis induction.


RESULTS
BGMP pretreatment (500 mg kg(-1) day(-1)) resulted in marked reduction of inflammatory injury, as assessed by lower extension of necrosis and damage score, myeloperoxidase, alkaline phosphatase, inducible nitric oxide synthase, interleukin 1beta, tumour necrosis factor and interleukin 17. These effects were generally comparable to those of 5-aminosalicylic acid (200 mg kg(-1) day(-1)). Neither compound affected the production of interferon gamma, tumour necrosis factor and interleukin 2 by mesenteric lymph node cells isolated from animals with ileitis. The expression of Foxp3 was increased in ileitis and not reduced significantly by BGMP or aminosalicylate treatment.


CONCLUSIONS
These results demonstrate that BGMP has anti-inflammatory activity in the ileum with similar efficacy to 5-aminosalicylic acid. The mechanism of action may involve Th17 and regulatory T cells and perhaps macrophages but probably not Th1 lymphocytes. Patients with Crohn's ileitis may benefit from treatment with BGMP.
Requena
P
P
Department of Biochemistry and Molecular Biology II, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), School of Pharmacy, University of Granada, Granada, Spain.
Daddaoua
A
A
Martínez-Plata
E
E
González
M
M
Zarzuelo
A
A
Suárez
M D
MD
Sánchez de Medina
F
F
Martínez-Augustin
O
O
D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002417:Cattle; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology*; D007079:Ileitis / Q000188:drug therapy* / Q000503:physiopathology; D020381:Interleukin-17 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D019804:Mesalamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid
D000893:Anti-Inflammatory Agents; D006020:Glycopeptides; D020381:Interleukin-17; D019804:Mesalamine; D014302:Trinitrobenzenesulfonic Acid