Review paper
Pro-inflammatory cytokines gene polymorphisms in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease, characterized by
a number of immunological disturbances and synovium involvement leading to joint destruction. The etiology is unclear, since the causal factor is still unknown. RA affect all ethnic groups. The frequency of the disease, depending on population, amounted about 0,5-2% and women are affected three times more frequently then men.
Genetic factors like HLA DRB1 and cytokine genes, play an important role in susceptibility and severity of the disease. In the pathogenesis of RA exist a hierarchy of cytokines expression, which favor the proinflammatory cytokines. Cytokines production is stimulated by the Th-cells. They control all phases of immune response: autocrine, endocrine and paracrine, but also play a key role in the inflammation. In the RA a pivotal role play IL-1 and TNF-α. TNF-α is responsible for the inflammatory and proliferative aspects, and IL-1 is responsible for the destructive aspects of RA. Other proinflammatory cytokines also play very important role in RA, because they are responsible for activation of enzymes in synovial fluid, which induce degradation of bone.
The determination of single nucleotide polymorphisms (SNP) of proinflammatory cytokines seems to be of great importance. Since we are dramatically lacking any prognostic factors for the development of RA, there is a possibility that SNPs may serve as the markers of susceptibility and severity of the disease.