Of the 44 patients included in the study Weisman were withdrawn 14, because the treatment is ineffective or induced side effects, including normal gastrointestinal Symptoms l Although Vargatef BIBF1120 slight improvements were observed offer, this Ver P38 changes the promise of future studies inhibitor. Pharmacological inhibitors of JNK, ERK1 / 2 and PI-3-kinase showed in vitro and in vivo efficacy of inhibiting the production of pro-inflammatory compounds. JNK inhibitor SP600125 specific reduced, not only the production of tumor necrosis factor, interferon ?, interleukin 6, and matrix metalloproteinase 2 COX, but also reduces the Gelenkzerst Tion in arthritis model adjuvant. Specific ERK1 / 2 inhibitor, Ro September 2210, the activation and proliferation and induces Tlymphocyte modest anti-inflammatory activity in various experimental models. To date, no human study has been initiated by these inhibitors. With JNK, it seems that the two isoforms have to be inhibited by an anti-inflammatory effect.
Mice who JNK2 gene protein expression of the transcription factor activator 1 is comparable to that of nozzles control-M. In contrast, decreased M Usen both JNK1 and JNK2 genes levels of activator protein 1 and collagenase Trichostatin A in synovial fibroblasts. In summary, the efficacy of anticytokine biologics in patients with inflammatory diseases of the bone, evidence that blocking the effects of a cytokine can slow a disease. In recent years, proposed the identification of proinflammatory signaling pathways of new therapeutic targets. Because these pathways are shared by several cytokines, their inhibition is probably as st Stronger than the current treatment strategies. Pharmacological inhibitors are evaluated in patients with rheumatoid arthritis With.
Although promising vorl INDICATIVE results were obtained only in a small number of patients. The key benefits of pharmacological inhibitors are easy to manage and co t low compared to gene therapy or biotherapy. After all, should enthusiasm by the merits of this new therapeutic family produced perhaps be tempered by the knowledge that the signal paths to contribute to physiological processes and its inhibition may be entered dinner side effects. Osteotrophic factors such as hormones, cytokines, growth factors and other molecules with a simultaneous improvement RANKL expression in stromal / osteoblasts. Sequentially, the mediator RANKL signal for osteoclastogenesis through RANK preosteoclast on cells. To summarize the interaction of RANKL / RANK is responsible for the differentiation and maturation of osteoclasts, Preferences Shore cells activate osteoclasts.
OPG acts as decoy receptor by osteoblast cells that binds RANKL expressed inhibits osteoclast development. Several studies have shown the opposite effect of RANKL and osteoprotegerin in modulating bone. overexpressing OPG and RANKL / M nozzles leads to osteopetrosis. Opposite Ph Genotype was usen in the expression of RANKL and osteoprotegerin / M That developed osteoporosis observed. In addition, several stimulators of bone resorption, such as to regulate the expression of RANKL osteoprotegerin inhibits expression in osteoblasts / stromal cells. In pathological bone resorption in hormonal St Changes observed inflammatory diseases and certain forms of cancer, the balance of this interaction is disturbed Rt.