Experimental Strategies in Autoimmunity: Antagonists of Cytokines and their Receptors, Nanocarriers, Inhibitors of Immunoproteasome, Leukocyte Migration and Protein Kinases

Abstract

Autoimmune diseases are a heterogeneous group of disorders and epidemiological studies demonstrate that their incidence is increasing worldwide. It is known that a complex interaction of genetic and environmental factors underlies their complex etiopathogenesis. In the light of the aforegoing the exact molecular key events were difficult to be explored; these represent the leading step to the prevention and treatment of autoimmune disorders. Novel therapeutic approaches are nowadays under investigation and specific treatments have been preferentially applied in experimental models of disease. New results were brought about and fascinating new pathways for treatment of autoimmunity were launched in the past years. Nevertheless novel targets for intervention, revealed to be successful in animal models, were not necessarily proven to be successful in humans, therefore were not necessarily introduced in clinical trials. In this review we present and discuss the results of novel therapeutic approaches and novel experimental strategies including antagonists of cytokines and cytokine receptors, Toll like receptors inhibitors, proteasome inhibitors, antisense oligonucleotides vehicled by nanocarriers, inhibitors of leukocyte migration, kinase inhibitors. We also present the results of ongoing trials in humans that rely on novel biologicals agents. These are presented as applied to organ and non-organ specific autoimmune disorders. In the future, novel therapeutic strategies will also combine different drugs that possibly intervene at different levels in which the immune system may be halted in its function.

Bortezomib followed by autologous stem cell transplantation in a patient with rheumatoid arthritis

“…[13] Indeed, Bortezomib attenuated both the acute phase and chronic phase of the inflammatory response and the severity of collagen-induced arthritis and ameliorate histological features in RA rats. [14] In healthy volunteers and RA patients, Bortezomib was demonstrated to be a rapid and potent inhibitor of NF-κB-inducible cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-10, by activating T cells. [15] In addition, Bortezomib displayed clear therapeutic efficacy in animal models of systemic lupus erythematosus, inflammatory bowel disease, myasthenia gravis, and arthritis.…”

Type 1 Diabetes and Its Multi-Factorial Pathogenesis: The Putative Role of NK Cells

“…By encountering the self- or cross-reactive antigen, Th cells activate, expand and differentiate into various effector subsets, including Th1, Th2 and T regulatory (Treg) cells (rev in [ 18 ]). The majority of CD4 + and CD8 + islet-infiltrating T cells exhibit a Th1 phenotype.…”

Case-control analysis of the <i>ERAP1</i> polymorphism rs30187 in Italian type 1 diabetes mellitus patients

“…Autoimmune diseases can affect different organs and tissues [1,2]. In these conditions, the breakdown in the balance between autoregulatory immune pathways and pathogenic autoreactivity leads to aggressive antibody and T-cell mediated reactions directed against antigens expressed by the host's own tissues [2].…”

“…In these conditions, the breakdown in the balance between autoregulatory immune pathways and pathogenic autoreactivity leads to aggressive antibody and T-cell mediated reactions directed against antigens expressed by the host's own tissues [2]. It is recognised that a complex interaction of genetic/environmental factors underlies the etiopathogenesis of autoimmune disorders [1,3]. Their incidence is increasing worldwide [2].…”