Impaired neutrophil chemotaxis in Crohn's disease relates to reduced production of chemokines and can be augmented by granulocyte-colony stimulating factor.
BACKGROUND
Defective neutrophil recruitment has been described as a primary pathogenic abnormality in Crohn's disease. Cantharidin-induced blisters provide a novel investigative tool to assess cellular influx and inflammatory mediator production during acute inflammation and allows the effects of therapy on these parameters to be measured.


OBJECTIVE
To determine whether reduced neutrophil tissue penetration in Crohn's disease relates to impaired production of inflammatory mediators, and whether it can be reversed by granulocyte-colony stimulating factor (G-CSF).


METHODS
Neutrophil and monocyte/macrophage populations and inflammatory mediators were measured in cantharidin blisters at 24 h. Neutrophil chemotaxis was assessed in vitro using blister fluid as the chemoattractant. The effect of s.c. G-CSF on blister phenotype was determined.


RESULTS
Significantly fewer neutrophils migrated into blisters in Crohn's patients. The production of neutrophil chemokines, but not other inflammatory mediators, was reduced. This significantly correlated with reduced chemotaxis in vitro. Differences were unrelated to caspase-recruitment domain 15 genotype. G-CSF significantly increased blister neutrophil concentrations in control subjects and Crohn's patients.


CONCLUSIONS
Reduced neutrophil migration during acute inflammation in Crohn's disease is associated with impaired production of appropriate chemoattractants. G-CSF therapy increases neutrophil tissue migration, which may partially account for its observed therapeutic effect.
Harbord
M W N
MW
Department of Medicine, University College London, London, UK. marcus.harbord@chelwest.nhs.uk
Marks
D J B
DJ
Forbes
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A
Bloom
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SL
Day
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RM
Segal
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D000328:Adult; D000368:Aged; D018925:Chemokines / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology*
D018925:Chemokines; D016179:Granulocyte Colony-Stimulating Factor