Increased production of granulocyte-macrophage colony-stimulating factor in Crohn's disease--a possible target for infliximab treatment.
BACKGROUND
The presence of neutrophils among epithelial cells is one of the major features of the inflammation in Crohn's disease, and has been used to indicate disease activity. The survival of neutrophils outside the blood vessels is limited and their longevity is influenced by granulocyte-macrophage colony-stimulating factor (GM-CSF), which probably reduces neutrophil apoptosis.


OBJECTIVE
To study GM-CSF production in intestinal cell cultures from Crohn's disease patients before and after infliximab treatment.


METHODS
Colonic mucosal biopsies were obtained from 29 Crohn's disease patients before and after three infliximab infusions (5 mg/ml) and from ten healthy subjects.


METHODS
Biopsies were cultured in RPMI at high concentrations of interleukin-2 (IL-2) (2000 U/ml) and IL-4 (500 U/ml), but without antigen addition. GM-CSF content was analysed after 5 days culture and related to the Crohn's disease activity index (CDAI) and compared with the GM-CSF production from healthy subjects. Peripheral leucocyte count, C-reactive protein and the degree of mucosal inflammation, evaluated histologically, were determined. In-vitro T cell GM-CSF production was studied with/without addition of infliximab and after stimulation.


RESULTS
GM-CSF production was increased in Crohn's disease patients compared with healthy controls (P = 0.02) and correlated with the CDAI (Spearman rho = 0.65, P = 0.001). GM-CSF levels and mucosal histology score decreased (P = 0.007 and P = 0.01 respectively) after three infliximab infusions, as did the peripheral blood leucocyte count (P < 0.001). Infliximab inhibited in-vitro T cell GM-CSF production.


CONCLUSIONS
In-vitro cell culture production of GM-CSF was increased in Crohn's disease and related to inflammation, but decreased after infliximab treatment, probably because intestinal T cell GM-CSF production was reduced.
Agnholt
Jørgen
J
Department of Medicine V, Aarhus University Hospital, DK-8000 Aarhus C, Denmark. jorge@akh.aaa.dk
Kelsen
Jens
J
Brandsborg
Birgitte
B
Jakobsen
Niels O
NO
Dahlerup
Jens F
JF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D016130:Immunophenotyping; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000069285:Infliximab