[Cell adhesion molecules in evaluation of Crohn's disease therapy].

ABSTRACT

The treatment of inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn's disease (CD) is one of actual problems of modern gastroenterology and coloproctology. In recent years a great attention is paid to the molecules of adhesion. Adhesion proteins play a significant role in the development of inflammation in patients with IBD. They cause the migration of cells from the capillaries into the center of inflammation, i.e. do much to increase the inflammatory infiltration of the mucosa and homing of lymphocytes. Changes in the levels of adhesion factors under the influence of biological therapy have been insufficiently studied. So the aim of our study was to determine the diagnostic value of adhesion molecules--integrin-sVCAM-1 and selectins P-, E-, L- for the assessment of the effectiveness of therapy in patients with UC and CD and prognosis of the disease. 15 patients with IBD were examined (15 patients with Crohn's disease (CD)). 9 patients were treated using infliximab 5 mg/kg according to the standard scheme (0-2-6 and then every 8 weeks). 3 patients with IBD received anti-inflammatory therapy with the introduction of the culture of MSC in the number of 150 x 108 cells suspended in 200 ml of physiological solution with the addition of heparin (10 IU/ml). 3 patients received azathioprine (2 mg/kg) and glucocorticosteroids (GCS) 1 mg/kg. The clinical symptoms, the level of leukocytes, erythrocyte sedimentation rate, C-reactive protein and also were analyzed before and after the treatment with infliximab and transplantation of MSC. The status of the colonic mucosa was evaluated using colonoscopy with biopsy. The concentration of adhesion molecules L-selectin, E-selectin, P-selectin, integrin-sVCAM-1 in blood serum was analyzed using immunoenzyme method twice before the beginning of treatment and after 2 months. It is established that after the standard therapy with the use of corticosteroids and azathioprine clinical and laboratory signs of IBD activity and increased levels of adhesion molecules remained in all patients. It is reliably determined that under the influence of infliximab the levels of P-selectin, E-selectin and integrin-sVCAM-1 decrease to 8.9 +/- 1.0 ng/ml, 5.5 +/- 1.7 ng/ml, 9.5 +/- 4.4 ng/ml, respectively (p < 0.001) in all patients with IBD. This point to the suppression of the synthesis of the main inflammatory cytokine alpha-TNF. Transplantation of MSC causes significant decrease of P-selectin, E-selectin to 6.9 +/- 1.1 ng/ml and 5.7 +/- 1.3 ng/ml, respectively (p < 0.001). Integrin-sVCAM-1 has decreased slightly to 12.2 +/- 2.2 ng/ml, p > 0.1. This is associated with the onset of the maximum therapeutic effect only in 1-2 months after transplantation. The levels of P-selectin, E-selectin, integrin-sVCAM-1, reflecting the acute phase of inflammation, decreased after MSC transplantation and infliximab induction therapy. The level of L-selectin, reflecting a chronic autoimmune inflammation, practically does not decrease after the MSC transplantation (8.9 +/- 0.5 ng/ml, p < 0.05) and infliximab induction therapy (9.6 +/- 0.8 ng/ml, p > 0.1). These include the appointment of long-term infliximab therapy and repeated MSC transplantations. P-selectin, E-selectin, L-selectin, integrin-sVCAM-1 are modern markers of inflammation and may be used to assess the effectiveness of standard and biological therapy in patients with IBD, and to predict the course of the disease.