Cytokines are indispensable signals of the mucosa-associated immune system for maintaining normal gut homeostasis. An imbalance of their profile in favour of inflammation initiation may lead to disease states, such as that is observed in inflammatory bowel diseases (IBD). Although Crohn's disease (CD) is often described as a prototype of T-helper 1-type diseases, and ulcerative colitis (UC) is traditionally viewed as a T-helper 2-mediated condition, the classic paradigm, which categorises cytokines into pro- and anti-inflammatory groups, has recently been changed. The inflammation regulatory pathways may not be mutually exclusive as individual cytokines can have diverse and even opposing functions in various clinical and immunological settings. None the less there are many common immunological responses in IBD that are mediated by cytokines. Although they regulate and influence the development, course and recurrence of the inflammatory process, the concrete pathogenic role of these small signaling molecules is sometimes not unambiguous in the subtypes of the disease. Our aim is to review the current information about pro- and anti-inflammatory effects of traditionally studied and recently discovered cytokines in the pathogenesis of UC and CD. The better understanding of their production and functional activity may lead to the development of new therapeutic modalities.

According to our study, aVD has a more prominent short-term beneficial effect on bone metabolism and disease activity in CD compared with pVD.

Nucleosomes are the dominant autoantigens in patients with systemic lupus erythematosus (SLE), and immune complexes involving nucleosomes are the major cause of tissue damage. The activity of DNase I, the enzyme responsible for nucleosome degradation, has been found to be decreased in patients with SLE. However, it is not known whether DNase activity is a clinically useful parameter. The aim of our study was to assess DNase activity in a prospective study of 113 patients with SLE in relation to disease activity and organ involvement. We included two control groups: 9 patients with undifferentiated connective tissue disease (UCTD) and 14 healthy individuals. DNase activity was found to be lower in patients with SLE (63.75% ؎ 12.1%) than in the controls (81.3% ؎ 9.25%) (P < 0.001). DNase activity in patients with UCTD (64.9% ؎ 18.2%; P ‫؍‬ 0.854) did not differ from that in patients with SLE. Patients with SLE had higher antinucleosome antibody titers (356.3 ؎ 851) than the controls (1.44 ؎ 2.77; P < 0.01) or UCTD patients (39.9 ؎ 57.7; P < 0.01). In addition, samples positive for antinucleosome antibodies displayed low levels of DNase activity. Within the SLE group, the presence of renal disease had no impact on DNase activity or antinucleosome antibody titers. Also, the SLE disease activity index showed no correlation with DNase activity. In a longitudinal study of six SLE patients, DNase activity did not follow disease activity or autoantibody titers. Our results confirm that serum DNase activity is decreased in patients with SLE, but we conclude that it is not a clinically useful parameter for the prediction of flare-ups of disease or renal involvement.Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of a wide range of pathological autoantibodies. Those directed against chromatin components, e.g., double-stranded DNA (dsDNA), histones, and the nucleosome, are of paramount pathological importance (6,8,20).Recent studies of patients with SLE suggest the increasing diagnostic importance of antinucleosome antibodies, in addition to antibodies directed against dsDNA (1, 17). These circulating antibodies may form immune complexes with their target antigens, the glomerular deposition of which will lead to the development of renal damage (12,14).The incidence of immune complex-mediated glomerulonephritis (GN) among SLE patients varies from 30 to 60%. Several studies have confirmed that autoantibodies are produced through an antigen-driven T-cell-dependent mechanism (13,23,27). According to this model, the defective clearance of apoptotic cell debris predisposes individuals to SLE through the accumulation of the chromatin components arising from the dying cells (5, 28).DNase I (pancreatic DNase) and DNase II (spleen acid DNase) cleave nucleosomal DNA, which promotes the disposal of circulating nuclear material. DNase I, a glycoprotein with a molecular mass of 30,400 Da, is a cation-binding secretory endonuclease that digests dsDNA in a sequence-dependent manner (24). DNase II,...

Colonic inflammation is required to heal infections, wounds, and maintain tissue homeostasis. As the seventh hallmark of cancer, however, it may affect all phases of tumor development, including tumor initiation, promotion, invasion and metastatic dissemination, and also evasion immune surveillance. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability, and, further, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Both sporadical and colitis-associated colorectal carcinogenesis are multi-step, complex processes arising from the uncontrolled proliferation and spreading of malignantly transformed cell clones with the obvious ability to evade the host’s protective immunity. In cells upon DNA damage several proto-oncogenes, including c-MYC are activated in parelell with the inactivation of tumor suppressor genes. The target genes of the c-MYC protein participate in different cellular functions, including cell cycle, survival, protein synthesis, cell adhesion, and micro-RNA expression. The transcriptional program regulated by c-MYC is context dependent, therefore the final cellular response to elevated c-MYC levels may range from increased proliferation to augmented apoptosis. Considering physiological intestinal homeostasis, c-MYC displays a fundamental role in the regulation of cell proliferation and crypt cell number. However, c-MYC gene is frequently deregulated in inflammation, and overexpressed in both sporadic and colitis-associated colon adenocarcinomas. Recent results demonstrated that endogenous c-MYC is essential for efficient induction of p53-dependent apoptosis following DNA damage, but c-MYC function is also involved in and regulated by autophagy-related mechanisms, while its expression is affected by DNA-methylation, or histone acetylation. Molecules directly targeting c-MYC, or agents acting on other genes involved in the c-MYC pathway could be selected for combined regiments. However, due to its context-dependent cellular function, it is clinically essential to consider which cytotoxic drugs are used in combination with c-MYC targeted agents in various tissues. Increasing our knowledge about MYC-dependent pathways might provide direction to novel anti-inflammatory and colorectal cancer therapies.

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