Cytokine provides new therapeutic target for inflammatory
bowel disease
The cytokine macrophage-migration inhibitory factor
(MIF) plays an essential role in the pathogenesis of Crohn's disease,
a new study shows. Intervention in MIF signalling could form a future
target for treatment of the disease, the researchers say.
Dr Ype de Jong, Beth Israel Deaconess Medical Centre,
Boston, and colleagues explain that colitis is dependent on interaction
between the mucosal immune system and intestinal bacteria. In colitis,
bacterial products, such as lipopolysaccharide, chronically stimulate
the immune system causing MIF to be secreted. The cytokine has a variety
of pro-inflammatory functions including overriding the immunosuppressive
effects of steroids and enhancing the production of tumour necrosis factor
and nitric oxide by immune cells.
The researchers examined plasma concentrations of
MIF in patients with active Crohn's disease and investigated MIF's role
in experimental colitis. They found that patients with Crohn's disease
had higher plasma MIF concentrations than healthy controls and that Crohn's
disease was responsible for increased plasma MIF.
They also found that murine colitis was dependent
on MIF produced by haematopoetic cells and MIF was required for disease
development in both acute and chronic mouse models of colitis. Administering
a monoclonal antibody that blocked MIF action prevented disease development
and reduced the severity of colitis, as well as suppressing established
colitis, they say (Nature Immunology 2001;2:1061).
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