Abatacept (Orencia)

From the decade of 1990 the advances in molecular biology have shown new approaches to the treatment for rheumatoid arthritis and after systemic inflammatory conditions associated to autoimmunity. The main approaches include agents that: · Interfere with the function of cytokines · Inhibit the "second signal" required for the activation of the T cells · Deplete the T cells T (Th) cells secrete specific cytokines that in turn influence or perpetuate systemic inflammation. Th cells and their cytokines can be divided in two subgroups, called Th1 and Th2. The cytokines generated by Th1 or Th2 inhibit the cellular function of the other phenotype, for example, Interlukin 10, a cytokine segregated by Th2 inhibits the cellular function of Th1 and interferon gamma and Interlukin 12 produced by Th1 inhibit the proliferation of Th2 cells. Many of the biological therapies that have been developed aim to lower pro-inflammatory response of Th1 or increase the anti-inflammatory production of Th2 cytokine. The Th1 lymphocytes participate in a wide variety of inflammatory processes such as rheumatoid arthritis, psoriasis, psoriatic arthritis, rejection of grafts, and others. The pro-inflammatory mediators produced by Th1cells include: · Interlukin (IL)-12 · Interferon gamma · TNF · IL-15 · IL-9 · IL-10 · Il-13 The Th2 lymphocytes stimulate the production of antibodies by the B cells and increase the eosinophilic response. Activation of Th2 cells contributes to the development of chronic rejection, systemic erythematosus lupus and systemic sclerosis. The mediators produced by Th2 cells include: · IL-4 · IL-5 · IL-9 · IL-10 · IL-13 The tumor necrosis factor (TNF) and Interleukin-1 beta (IL-1) are two cytokines that intervene in the pathogenesis of rheumatoid arthritis and other chronic inflammatory conditions. When they are secreted by the synovial macrophages, TNF and IL-1 stimulate the proliferation of the synovial cells and the production of collagenase inducing the degradation of the cartilage, the resorption of the bone and inhibits the repair of the cartilage. TNF and IL_1 induce the molecular expression of cell adhesion resulting in intensification and release of additional cytokines such as IL-6, additional IL-1 and metabolites of arachidonic acid. The TNF inhibitors have been approved by FDA for the treatment of some rheumatic diseases. Abatacept (CTLA4-Ig) is a protein of soluble fusion that is formed by the Antigen 4 of the lymphocytes T and by the portion Fc of IgG1 that prevents or decreases the arthritis associated to the collagen. <a id="