Direction of new drug research: soft regulation of inflammatory immune responses

摘要

Inflammation reaction and immune response are inseparable at the levels of system, tissue, cell and molecule. Inflammatory immune responses (IIR) is defined a moderate or abnormal system responses of inflammatory immune related cells in responding to the internal and external environ-ment changes of body. Inflammatory immune related cells (traditionally, eg, macrophages, dendritic cells, T cells and B cells, etc, and non- traditionally, eg, glial cells, endothelial cells, epithelial cells, fibroblasts, synovial cells and liver cells, etc), and cytokines/receptor signal transduction involved in IIR. In current clinic drugs, such as inhibitors of COXs, inhibitors of TNF-alpha, IL-6, IL-17, BAFF etc, tradi?tional immunosuppressive drugs (eg, methotrexate, leflunomide) and novel kinase inhibitor (eg, JAKs inhibitor), suppress enzyme activity, gene synthesis and transcription, cytokines and receptor signal, etc, respectively. These drugs restrain the excessive activation function of inflammatory immune related cells, but at the same time, also inhibit the physiological response of these cells to signaling molecules, which cause physiological function disorder of cells and tissues, increase the risks of serious adverse drug reaction including infection and cancer. Soft regulation of inflammatory immune responses (SRIIR), that is regulating the activity of key molecules or interaction between molecules in cells and resulting in making excessive activation function back to normal physiological levels, is a novel direction of discovery and development of new drugs for the treatment of IIR related diseases.