Predictive value of mucosal TNF-alpha transcripts in steroid-refractory Crohn's disease patients receiving intensive immunosuppressive therapy.
BACKGROUND
Concentrations of proinflammatory cytokines are increased in the intestinal mucosa of patients with active Crohn's disease (CD). In a prospective study we investigated whether cytokines can predict long-term remission (>6 months) in patients with steroid-refractory CD receiving treatment with infliximab or cyclophosphamide, followed by azathioprine or methotrexate.


METHODS
Cytokine transcripts were quantified using real-time polymerase chain reaction (PCR) in mucosal biopsies from 19 patients with active, steroid-refractory CD before and 8 weeks after initiation of therapy. Patients were treated with cyclophosphamide (monthly treatment of 750 mg cyclophosphamide intravenously) or infliximab (5 mg/kg body weight) and were followed until relapse of the disease. Statistical analysis was performed to identify predictive factors to discriminate between patients with or without long-term remission.


RESULTS
Seventeen out of 19 patients achieved remission of the disease, two patients were nonresponders, while six out of 17 patients exhibited an early recurrence. Pretreatment TNF-alpha, IL-18, MRP-14, and IL-8 transcripts were significantly correlated with long-term remission. While several cytokines, most importantly MMP-1, determined after 8 weeks were able to predict patients achieving long-term remission, only a decrease of TNF-alpha levels after 8 weeks was predictive. Overall, statistical analysis identified lower pretreatment TNF-alpha levels as the strongest predictor of long-term remission among baseline variables.


CONCLUSIONS
Quantification of mucosal TNF-alpha transcripts prior to therapy allows identification of patients achieving long-term remission upon immunosuppression with infliximab or cyclophosphamide. Real-time PCR might have considerable potential in the analysis of disease activity and subsequent clinical management of patients with immunosuppressive therapies.
Schmidt
Carsten
C
Department of Internal Medicine II, Friedrich Schiller-University, Jena, Germany.
Giese
Thomas
T
Hermann
Eva
E
Zeuzem
Stefan
S
Meuer
Stefan C
SC
Stallmach
Andreas
A
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018925:Chemokines / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism; D003520:Cyclophosphamide / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018925:Chemokines; D016207:Cytokines; D005765:Gastrointestinal Agents; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D003520:Cyclophosphamide; D011239:Prednisolone; D000069285:Infliximab