The proinflammatory CXC-chemokines GRO-alpha/CXCL1 and MIG/CXCL9 are concomitantly expressed in ulcerative colitis and decrease during treatment with topical corticosteroids.
BACKGROUND
Ulcerative colitis is characterized by relapsing mucosal inflammation where the lesions include tissue-damaging granulocytes. In addition, T cells and natural killer (NK) cells play important pathophysiologic roles. Chemokines are a large family of peptides that play key roles in the regulation of inflammation. The CXC-chemokines, growth-related oncogene (GRO)-alpha/CXCL1 and interleukin (IL)-8/CXCL8, both recruit neutrophils and possess mitogenic properties, whereas the interferon-dependent CXC-chemokines monokine induced by gamma-interferon (MIG)/CXCL9, interferon-gamma inducible protein of 10 kD/CXCL10, and IFN-inducible T cell alpha chemoattractant/CXCL11 recruit and activate T cells and NK cells.


METHODS
The expression of CXC-chemokines was studied in eight controls and in 11 patients suffering from ulcerative colitis in the distal part of the colon, before and during topical treatment with corticosteroids. Perfusates (obtained before, after 7 days, and after 28 days of treatment) and pinch biopsies (obtained before and after 28 days of treatment) were collected by colonoscopy. The rectal release of GRO-alpha and MIG was determined by enzyme-linked immunosorbent assay (ELISA), and tissue expression of the chemokines was detected in colonic tissue by immunohistochemistry.


RESULTS
In perfusates, high levels of GRO-alpha, IL-8, and MIG were detected compared with controls (p=0.02, 0.005, and p=0.03, respectively). During treatment with corticosteroids, both GRO-alpha and MIG decreased. In clinical nonresponders, characterized by sustained inflammation, the levels of GRO-alpha and MIG remained elevated. Both epithelial cells and granulocytes, present in the submucosa, expressed GRO-alpha and MIG as detected by immunohistochemistry.


CONCLUSIONS
CXC-chemokines are likely to be important in the pathophysiology of ulcerative colitis and may become targets for novel treatment strategies. In addition, GRO-alpha may serve as a marker of disease activity.
Egesten
Arne
A
Department of Clinical Sciences Lund, BMC B14, Tornavagen 10, 221 84, Lund, Sweden. Arne.Egesten@med.lu.se
Eliasson
Mette
M
Olin
Anders I
AI
Erjefält
Jonas S
JS
Bjartell
Anders
A
Sangfelt
Per
P
Carlson
Marie
M
D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000378:metabolism*; D054357:Chemokine CXCL10 / Q000378:metabolism; D054370:Chemokine CXCL9 / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D003113:Colonoscopy; D015536:Down-Regulation; D004733:Enema; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage*; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010477:Perfusion / Q000379:methods; D011239:Prednisolone / Q000008:administration & dosage*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; C475829:CXCL1 protein, human; C114753:CXCL10 protein, human; C080810:CXCL9 protein, human; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D005765:Gastrointestinal Agents; D016209:Interleukin-8; D011239:Prednisolone
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