Conclusions

Cure Arthritis Naturally

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The alternative signaling pathway of IL-6 via the sIL-6R/IL-6 complex seem to be an important mechanism for the development of chronic inflammatory diseases and inflammation-associated tumor growth. The ability of selective inhibition of sIL-6R-dependent IL-6 responses with sgp130 can be used in vivo to distinguish between classical IL-6 signaling and IL-6 trans-signaling (Fig. 4). There is now clear evidence that chronic inflammatory states often lead to neoplastic lesions. Sgp130 can be used to effectively block immunological processes that promote inflammatory disease progression. One clear advantage of selectively blocking IL-6 trans-signaling is the fact that classic IL-6 responses remain unaffected. These include the hepatic acute-phase response, which plays an important role in the defense of the body against infections and trauma. These

Epithelial

Fig.3a-c Schematic model of TGF-|-regulated IL-6 trans-signaling in experimental colon cancer. a A reduction of TGF| signaling results in increased IL-6 secretion. b The observed upregulation of the ADAM17 metalloproteinase on epithelial cells results in shedding of the IL-6R. Upon stimulation with the IL-6/sIL-6R complex, T cells become resistant to apoptosis and therefore the number of T cells increases. c Growth of epithelial cells in tumor lesions is observed upon stimulation with the IL-6/sIL-6R complex. Tumor growth can be inhibited by blocking the IL-6R using a monoclonal antibody or by inhibiting IL-6 trans-signaling with the sgp130Fc protein. Dark grey symbols, gp130; black symbols, membraned bound IL-6R and soluble IL-6R; light grey symbols, epithelial cells

Fig.3a-c Schematic model of TGF-|-regulated IL-6 trans-signaling in experimental colon cancer. a A reduction of TGF| signaling results in increased IL-6 secretion. b The observed upregulation of the ADAM17 metalloproteinase on epithelial cells results in shedding of the IL-6R. Upon stimulation with the IL-6/sIL-6R complex, T cells become resistant to apoptosis and therefore the number of T cells increases. c Growth of epithelial cells in tumor lesions is observed upon stimulation with the IL-6/sIL-6R complex. Tumor growth can be inhibited by blocking the IL-6R using a monoclonal antibody or by inhibiting IL-6 trans-signaling with the sgp130Fc protein. Dark grey symbols, gp130; black symbols, membraned bound IL-6R and soluble IL-6R; light grey symbols, epithelial cells

Global IL-6 Neutralization

Applications (positive clinical trial data) Rheumatoid arthritis Juvenile rheumatoid arthritis Castleman's disease Crohn's disease

Selective blockade of IL-6 trans-signaling

Blocks effector T-cell functions

Regulates leukocyte recruitment

Governs leukocyte apoptosis

Modulates inflammatory chemokines

Some evidence of dual regulation of T-cell responses by IL-6 and IL-6 trans-signaling

Fig. 4 Therapeutic strategies for targeting IL-6 signaling. Current therapeutic regimes designed to clinically suppress IL-6 activities involve the application of the blocking monoclonal antibody MRA (atlizumab, tocilizumab) effective against a range of conditions. This did not distinguish between classical IL-6 signaling and IL-6 trans-signaling. The fusion protein sgp130Fc selectively targets IL-6 trans-signaling, and leaves classical IL-6 signaling intact considerations have provided a therapeutic rationale for the administration of sgp130 in a series of chronic inflammatory conditions, which are prone to progress to cancer.

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Osteoarthritis

Osteoarthritis

Thank you for deciding to learn more about the disorder, Osteoarthritis. Inside these pages, you will learn what it is, who is most at risk for developing it, what causes it, and some treatment plans to help those that do have it feel better. While there is no definitive “cure” for Osteoarthritis, there are ways in which individuals can improve their quality of life and change the discomfort level to one that can be tolerated on a daily basis.

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