Proinflammatory cytokines underlying the inflammation of Crohn's disease.
OBJECTIVE
To encapsulate our current understanding of the proinflammatory cytokines responsible for the inflammation underlying Crohn's disease and the prospect of using this information to devise therapy for this condition based on inhibition of these cytokines.


RESULTS
Current research is shedding new light on the role of both T helper cell (Th)1 and Th17 responses in the pathogenesis of Crohn's disease. Initial studies conducted a decade ago highlighted the view that Crohn's disease inflammation is caused by an interleukin-12-driven Th1 response, which resulted in the generation of interferon-gamma, which then served as the main inflammatory mediator. In recent years, however, this view has been largely eclipsed by studies, conducted mainly in murine models, showing that a Th17 response is the main cause of Crohn's disease inflammation through the production of interleukin-17. Now, a somewhat more balanced view is emerging, which holds that interferon-gamma is still a major proinflammatory cytokine in Crohn's disease, although it may arise from both the Th1 and Th17-mediated responses at different phases of the inflammatory process.


CONCLUSIONS
The new findings continue to support the idea that anti-interleukin-12p40, an antibody that inhibits both the Th1 and Th17 response, is logically the most potent anticytokine for the treatment of Crohn's disease.
Strober
Warren
W
Mucosal Immunity Section, Laboratory of Host Defenses, NIAID, Bethesda, Maryland 20892-6612, USA. Wstrober@niaid.nih.gov
Zhang
Fuping
F
Kitani
Atsushi
A
Fuss
Ivan
I
Fichtner-Feigl
Stefan
S
D000818:Animals; D003424:Crohn Disease / Q000276:immunology*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D053759:Interleukin-23 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D008233:Lymphotoxin-alpha / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D000097043:Interleukin-22
D016207:Cytokines; D018664:Interleukin-12; D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D008233:Lymphotoxin-alpha; D000097043:Interleukin-22
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