There is evidence of a disbalance in the inflammatory regulation of patients with inflammatory bowel diseases (IBD). Interleukin-1 beta plays an important role in the pro-inflammatory response. Our aim was to study the influence which IL1B gene polymorphisms may have on the severity and course of these diseases. Ninety-six patients with ulcerative colitis (UC), 98 patients with Crohn's disease (CD), and 132 ethnically matched healty individuals (HC) were typed for the polymorphic sites in the promoter region (position -511) and in exon 5 (position +3953) of the IL1B gene, using polymerase chain reaction (PCR)-based methods. In the CD group a significant association (P = 0.009) was found in this pair of genes. Homozygotes for allele 1 at position +3953 were more often present (69% vs 31%) in the subgroup of patients carrying at least one copy of allele 2 at position -511. This association was significant in patients with non-perforating disease (P = 0.002), but was not present in patients with perforating-fistulizing disease. The distribution of both allelic pairs in the non-fistulizing group proved to be significantly different from HC (P < 0.05), UC (P < 0.03), and the fistulizing group (P < 0.05). There was a similar association in non-operated patients (P = 0.024), whereas no such association was found in surgically treated patients. Among carriers of allele 2 at position -511, UC patients with more severe bleeding symptoms (P = 0.006) were less frequently found. These results suggest that IL1B gene polymorphisms participate in determining the course and severity of inflammatory bowel disease and contribute to explain the heterogeneity of these diseases.

Our results show that, at least in some white populations, the contribution of the cytokine gene polymorphisms evaluated in this study (IL-1B, IL-1RN, IL-12p40, LTA, IL-10, IL-4, and TGF-B1) to GC susceptibility may be less relevant than previously reported.

IL-1RA and IL-1beta are disease severity genes rather than disease susceptibility genes. Furthermore, these gene polymorphisms may define subgroups of patients with a worse prognosis.

Similar to other chronic inflammatory diseases, AS is associated with the IL-1RN*2 allele. Further studies are necessary to determine the biological significance of these findings in relation to susceptibility or severity of the disease.

A small proportion of patients infected with Helicobacter pylori or using non-steroidal anti-inflammatory drugs (NSAIDs) develops peptic ulcer disease. Since family studies have shown the importance of the genetic background of the host in the development of gastric and duodenal ulcers, immunogenetic factors involved in the regulation of inflammation deserve further study. Polymorphisms in the genes encoding tumour necrosis factor (TNF) and lymphotoxin-alpha (LTA) have been shown to contribute to the severity of infectious disease. Our aim was to study four bi-allelic polymorphisms in the TNF and LTA genes, which occur as five haplotypes, in patients with peptic ulcer disease. A total of 130 patients with duodenal ulcer, 50 with gastric ulcer and 102 ethnically-matched Spanish Caucasian healthy controls were studied. H. pylori infection was determined by invasive and non-invasive tests. Odds ratios were obtained by logistic regression analysis. H. pylori was detected in 91.8% of peptic ulcer patients and in 73.3% of controls (P < 0.001). Patients with gastric ulcer had a lower frequency of the TNF-308 allele 2 and a higher frequency of the LTANcoI 2.2 genotype when compared with duodenal ulcer patients (P < 0.01 and P = 0.03, respectively). Carriers of haplotype TNF-I were more frequent in gastric ulcer patients (49%) than in controls (28%) (P < 0.05) and the haplotype TNF-E was significantly more frequent in duodenal ulcers than in gastric ulcers (27% vs 8.2%; P < 0.01). Logistic regression analysis identified haplotype TNF-I carrier status as an independent risk factor for peptic ulceration in H. pylori-infected patients (OR: 4.2; 95%CI: 1.7-10.2). These results suggest that TNF and LTA gene polymorphisms are related to the development of gastric and duodenal ulcer and may determine disease outcome in H. pylori infection.