Abstract
agents. Therapeutic action of anti-TNF turns to blockade proinflammatory cytokines cascade. Under pressure of microbial antigens antigen-presenting cells activates and secretes IFN-G and IL-2. IL-2 promotes clonal expansion of T-cells with Th-1 and Th-2 differentiation. Th-2 cells produce cytokines (IL-4, 5, 6, 10, 13) one of them IL-10 suppress activity of Th-1 and inhibits cellular immune response. Besides bacterial lipopolisacharides activate monocytes and lead to the induction of cytokines TNF, IL-1, 10, 12. These cytokines are also produced by transmembrane TNF-bearing macrophages in inflammatory sites. Infliximab administration inhibit production TNF IL-1 but not IL-10 in these cells. IL-10 concentration relatively increase after infliximab course. During and after anti-TNF therapy not only anti-TNF antibodies has been found but also autoantibodies, antinuclear, anticardiolipine antibodies and other. We evaluated level of IL-10 in patients with TNF therapy. 47 IBD patients (28 UC, 19 CD) who have received infliximab 5mg/kg in moderate stage of disease were studied. Before treatment all of them had CRP levels more than 5mg/l and TNF levels more than 2 norms. Retrospectively before the treatment two new biomarkers were analyzed: level of IL-10 less than norm and ratio of TNF to IL-10 more than 3 norms. In 7 (14.9%) IBD patients lost response to anti-TNF therapy were observed. Among them 6 (85.6%) had IL-10 level more or equal to norm before treatment and all of patients who lost response to infliximab had ratio TNF/IL-10 less than 3 norms. Clinical occurrences where cross-over and auto-antibody have important pathogenic role are extra intestinal manifestations (EIM). We analyzed EIM presents in 332 patients with IBD. Among them were 220 patients with UC and 112 CD patients. EIM in 89 (40.4%) UC patients and 55 (49.1%) patients with CD were found. Monorganic EIM in 63 (18.9%) patients and polyorganic in 86 (25.9%) were observed. Privilege cytokines profile changes in IBD patients with EIM were analyzed. Maximal increasing of IL-1 and TNF with decreasing IL-10 in plasma in patients with joints and cardiac EIM were observed. Conclusions: IL-10 is a perspective biomarker for identification response to anti-TNF-a agent. Joints extra-intestinal manifestations in IBD is one of clinical criteria to anti-TNF-a therapy.
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