IL-1 is one of the key mediators involved in the pathogenesis of rheumatoid arthritis (RA) and is known to affect the level of gene expression in various settings.
IL-1 may be one of these candidates because it has a central role in animal models of arthritis, and inhibition of IL-1 is used as a therapy of human RA.
IL-1 is a cytokine that exerts a pivotal role in innate immunity and in the pathogenesis of some autoimmune diseases, such as rheumatoid arthritis, and in autoinflammatory disorders, as familial Mediterranean fever and cryopyrin-associated periodic syndromes.
A prospective study in RA-group 2 demonstrated that the extent of joint destruction over 12 years was higher in patients genotyped heterozygous for the IL-1 A + 4845, IL-1B + 3953 and IL-1RN + 5111 SNPs compared to homozygous wildtype patients, although differences did not reach statistical significance.
Also, this study was conducted to explore the linkage between interleukin-1 (IL-1) receptor antagonist gene (IL-1RN) polymorphism, proinflammatory cytokine, and RA.
Also, we found three negative associated haplotypes with PE: IL-1α + 4845 G/IL-1β -511 A, IL-1β + 3954 C/IL-1β -511 A and interestingly IL-1α -889 C/IL-1β -511 A also with a positive association with RA.
Although early clinical results in rheumatoid arthritis (RA) suggested that RA is not primarily an IL-1-driven disease, the discovery that the rare genetic conditions called cryopyrin-associated periodic syndromes (CAPS) were caused by overproduction of IL-1 led to clinical development and approval for these conditions.
Although the resulting clinical and pathologic abnormalities are clearly T cell-dependent, macrophage and fibroblast cytokines such as IL-1 and TNF-alpha are required for full expression of the disease.The studies of Hata et al. raise the intriguing possibility that traditional proinflammatory cytokine networks represent common effector mechanisms in inflammatory joint diseases such as rheumatoid arthritis.
Anakinra (IL-1 receptor antagonist) and tocilizumab (monoclonal IL-6 receptor antibody) are two known anti-inflammatory agents successfully used in the treatment of inflammatory states like rheumatoid arthritis.
Anakinra, the recombinant form of IL-1 receptor antagonist (IL-1Ra), has been approved for clinical use in the treatment of rheumatoid arthritis as the drug Kineret trade mark, but it must be administered daily by subcutaneous injection.
Biological activity of IL-1 determined by mouse thymocyte proliferation assay was also enhanced by 50% in response to TGF-beta1 in the culture supernatant of RA FLS.
Blocking TNFalpha in RA results in down regulation of IL1beta mRNA at the systemic level and in reduction of the endogenous antagonists for IL1 and TNF and of other cytokines related to the acute phase response, such as IL6, within days.
Cadherin-11 expression was examined in the synovium of mice with CIA, of IL-1 receptor antagonist (IL-1Ra)-deficient mice and of patients with RA and osteoarthritis (OA).
Chondrocytes, stimulated by IL-1 and/or TNF alpha, are potential contributors to the elevated levels of LIF observed in the synovial fluids of patients with rheumatoid arthritis and other inflammatory arthritides.
Comparison was also made between IL-1 polymorphism and parameters of bone mineral metabolism and between patients with the HLA-DRB1 RA motif plus IL-1 beta 2 and patients without the two alleles.