Current and novel anti-inflammatory drug targets for inhibition of cytokines and leucocyte recruitment in rheumatic diseases

Abstract

Objectives Many studies of disease state mechanisms reveal that unbridled inflammation is to blame for many of the symptoms associated with autoimmune diseases such as Crohn’s and Rheumatoid Arthritis (RA). While therapies aimed at decreasing levels of pro‐inflammatory cytokines exist, some have failed clinically or have extensive adverse effects. The aim of this review is to discuss common drug targets for anti‐inflammatory therapies as well as explore potential mechanisms of action for new therapies. Various studies done on novel mechanisms targeting pro‐inflammatory cytokine release as well as leukocyte chemotaxis have been researched for discussion here. Both of these contribute to tissue injury and patient symptoms in inflammatory and autoimmune disease states. Key findings While many current drug targets suppress inflammation via the receptor, research aimed at identifying new compounds and signaling mechanisms is ongoing to identify new targets within pro‐inflammatory signaling pathways, or specific immune cell types. Conclusions While glucocorticoids and monoclonal antibodies have shown to be efficacious, some patients have encountered mixed results. Biologic therapies also come with a high price tag Thus, novel compounds with new immune drug targets are ideal for patients whose therapies have not been successful.

Aiding and Abetting Anhedonia: Impact of Inflammation on the Brain and Pharmacological Implications

“…Also relevant to their efficacy in reducing depressive symptoms in autoimmune and inflammatory disorders, there is a vast array of other anticytokine therapies that selectively target T-cell cytokines including anti-IL-17 and anti-IL-12/23, which drives TH1 polarization (Griffiths et al, 2017;Wittenberg et al, 2020), as well as drugs that target downstream cytokine signaling pathways, such as baricitinib, which inhibits Janus kinase (JAK) 1 and JAK2 (Szollosi et al, 2018), and multiple drugs that inhibit p38 MAPK (Lee and Kim, 2017). Other relevant drugs in development include those that inhibit TLR-4 signaling and inhibitors of cell adhesion molecules and chemokine receptors, of which two drugs are Federal Drug Administration (FDA)-approved, including maraviroc, which inhibits C-C chemokine receptor 5 for prevention of human immunodeficiency virus, and plerixafor, an antagonist to C-X-C chemokine receptor 4 used to mobilize stem cells (Szollosi et al, 2018). In addition, drugs that can inhibit inflammasome activation via the P2X7 receptor are also being explored.…”

γδ cells and tumor microenvironment: A helpful or a dangerous liason?

“…Therefore, beyond the basic immunology issues to be resolved, future research should aim at finding clinical‐grade tools to remove conditions determining IL‐17 γδ T cells polarization in the tumor microenvironment. One attractive prospect is to interfere with de novo differentiation of IL‐17 T cells by inhibiting polarizing cytokines with monoclonal antibodies (mAbs): thus, mAbs anti‐IL‐1β, IL‐6, or IL‐23, which are already on the market for the therapy of chronic inflammatory and autoimmune diseases, might prove helpful . An alternative should be the use of drugs which selectively antagonize RORC , the IL‐17 lineage‐specifying transcription factor .…”

“…thus, mAbs anti-IL-1 , IL-6, or IL-23, which are already on the market for the therapy of chronic inflammatory and autoimmune diseases, might prove helpful. 76 An alternative should be the use of drugs which selectively antagonize RORC, the IL-17 lineage-specifying transcription factor. [77][78][79] Importantly, these strategies would affect not only on T cells but also any other IL-17-producing cell.…”

Polymer/Nanoceria Hybrid Polyplexes for Gene and Antioxidant Delivery

“…Monoclonal antibodies targeting PD-1 can stimulate the immune system, while PD-1 inhibition can suppress its activity. Furthermore, therapies focusing on the inhibition of pro-inflammatory cytokines are also used with varying degrees of success to treat inflammation . Combining an antioxidant with genetic therapies targeting such genes could offer powerful anti-inflammatory response with simultaneous reduction of oxidative stress.…”

“…Furthermore, therapies focusing on the inhibition of pro-inflammatory cytokines are also used with varying degrees of success to treat inflammation. 11 Combining an antioxidant with genetic therapies targeting such genes could offer powerful anti-inflammatory response with simultaneous reduction of oxidative stress. Several gene therapies targeting ROS-generating sources have been shown to be effective in reducing oxidative stress in cells.…”