Autoimmune diseases (AIDs), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogrensyndrome (SS), multiple sclerosis (MS), inflammatory bowel disease (IBD), ankylosing spondylitis (AS), psoriasis, and so on, are increasingly becoming the major cause of global health burdens. Inflammatory reactions and abnormal immune responses are involved in the pathogenesis of AIDs. Immune related cells (traditionally, e.g., macrophages, dendritic cells, T cells and B cells, etc., and non-traditionally, e.g., glial cells, endothelial cells, epithelial cells, fibroblasts, synovial cells and liver cells, etc.), cytokines (TNF -alpha, IL-1, 2, 4, 6, 8, 10, 17, BAFF, PGE, TGF-beta, etc.) and signal transduction (G protein coupled receptors signaling, TNF-alpha- TRADD-TRAF2 signaling, Ras-MARPK- NF-?B signaling, BAFF-BAFFRs- -NF-?B signaling, etc.) play crucial roles in the inflammatory immune responses of AIDs.
In current clinics, drugs for AIDs include non-steroidal anti-inflammatory drugs (NSAIDs), steroidal anti-inflammatory drugs (SAIDs), disease-modifying antirheumatic drugs (DMARDs), biological agents, traditional Chinese medicine and natural medicine. These drugs suppress enzyme activity, gene synthesis and transcription, cytokines and receptor signal, etc, respectively. Therapeutic effects for these drugs are achieved by regulating inflammatory reactions and abnormal immune response involving in AIDs. The introduction of anti-TNF therapeutics has revolutionized the management of AIDs, such as RA, psoriatic arthritis (PsA), AS, IBD and ulcerative colitis (UC). Nevertheless, up to 40% of patients have no response to anti-TNF treatment.
Although effective in the treatment of AIDs, some drugs have some undesirable and adverse effects, for example the adverse effects of ulcers, kidney injury, and bleeding in NSAIDs treatment. TNF alpha treatment is associated with some adverse effects such as increased risk of infection and tumors. Inhibitors of TNF alpha, IL-6, IL-17, BAFF etc., DMARDs (e.g., methotrexate, leflunomide, ) and novel kinase inhibitors (e.g., JAKs inhibitor), restrain the excessive activation function of inflammatory immune related cells, also inhibiting the physiological response of these cells to signaling molecules, which cause physiological function disorders of cells and tissues, increasing the risks of serious adverse drug reactions.
Soft regulation of inflammatory immune responses (SRIIR), that is regulating the activity of key molecules or interactions between molecules in cells and resulting in reducing excessive activation of function back to normal physiological levels, is a novel direction of discovery and development of new drugs for the treatment of AIDs.
Autoimmune diseases (AIDs), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogrensyndrome (SS), multiple sclerosis (MS), inflammatory bowel disease (IBD), ankylosing spondylitis (AS), psoriasis, and so on, are increasingly becoming the major cause of global health burdens. Inflammatory reactions and abnormal immune responses are involved in the pathogenesis of AIDs. Immune related cells (traditionally, e.g., macrophages, dendritic cells, T cells and B cells, etc., and non-traditionally, e.g., glial cells, endothelial cells, epithelial cells, fibroblasts, synovial cells and liver cells, etc.), cytokines (TNF -alpha, IL-1, 2, 4, 6, 8, 10, 17, BAFF, PGE, TGF-beta, etc.) and signal transduction (G protein coupled receptors signaling, TNF-alpha- TRADD-TRAF2 signaling, Ras-MARPK- NF-?B signaling, BAFF-BAFFRs- -NF-?B signaling, etc.) play crucial roles in the inflammatory immune responses of AIDs.
In current clinics, drugs for AIDs include non-steroidal anti-inflammatory drugs (NSAIDs), steroidal anti-inflammatory drugs (SAIDs), disease-modifying antirheumatic drugs (DMARDs), biological agents, traditional Chinese medicine and natural medicine. These drugs suppress enzyme activity, gene synthesis and transcription, cytokines and receptor signal, etc, respectively. Therapeutic effects for these drugs are achieved by regulating inflammatory reactions and abnormal immune response involving in AIDs. The introduction of anti-TNF therapeutics has revolutionized the management of AIDs, such as RA, psoriatic arthritis (PsA), AS, IBD and ulcerative colitis (UC). Nevertheless, up to 40% of patients have no response to anti-TNF treatment.
Although effective in the treatment of AIDs, some drugs have some undesirable and adverse effects, for example the adverse effects of ulcers, kidney injury, and bleeding in NSAIDs treatment. TNF alpha treatment is associated with some adverse effects such as increased risk of infection and tumors. Inhibitors of TNF alpha, IL-6, IL-17, BAFF etc., DMARDs (e.g., methotrexate, leflunomide, ) and novel kinase inhibitors (e.g., JAKs inhibitor), restrain the excessive activation function of inflammatory immune related cells, also inhibiting the physiological response of these cells to signaling molecules, which cause physiological function disorders of cells and tissues, increasing the risks of serious adverse drug reactions.
Soft regulation of inflammatory immune responses (SRIIR), that is regulating the activity of key molecules or interactions between molecules in cells and resulting in reducing excessive activation of function back to normal physiological levels, is a novel direction of discovery and development of new drugs for the treatment of AIDs.
