Advances in the Treatment of Autoimmune Diseases; Cellular Activity, Type-1/Type-2 Cytokine Secretion Patterns and their Modulation by Therapeutic Peptides

Abstract

Autoimmune diseases are many, have an overall prevalence of about 3% of the world population, affecting more women than men, and their incidence is influenced by genetics and the environment. It is currently thought that the immune response of a genetically predisposed individual to an environmental pathogen, under the influence of inadequate or non-functional immunoregulatory mechanisms, can lead to the development of an autoimmune disease. Advances in the treatment of autoimmune diseases follow a better understanding of the abnormalities in the cellular activity pathways and the resulting, often permanent, imbalance of the pro- and anti-inflammatory cytokine expression profiles. Over the past few years, there has been a dramatic change in the therapeutic regimens employed in autoimmune diseases, with soluble receptors, monoclonal antibodies and molecular mimetics enhancing or gradually replacing conventional immunosuppressive therapies. New biologicals have been developed, targeting defined pathways of the adaptive immune response. One approach towards the therapeutic management of autoimmune diseases involves the design and use of peptide analogs of disease-associated epitopes to be used as immunomodulatory drugs. Peptides can target cell-functions directly, by interfering with the formation of the tri-molecular complex MHC-Peptide-TCR, and/or they can target soluble mediators such as cytokines or their receptors, eventually replacing monoclonal antibody therapies. This review offers an update on the treatment modalities of certain prototypic autoimmune diseases, based on the current knowledge of disease pathogenesis, with emphasis on cell activation and cytokine expression profiles.

Galectin-9 Induced Myeloid Suppressor Cells Expand Regulatory T Cells in an IL-10-Dependent Manner in CVB3-Induced Acute Myocarditis

“…This molecule, which is a natural product of cell types such as several cells of the innate immune system, endothelial cells, and epithelial cells, acts as a ligand to the inhibitory molecule Tim-3. Tim-3 is expressed on the surface of both Th17 cells and Th1 cells which are critically involved in initiation of inflammatory and autoimmune disease [41]. Zhu et al , have revealed that the Tim-3-galectin-9 pathway has evolved to ensure effective termination of effector Th1 cells [20].…”

The Treatment of Multiple Sclerosis with Inosine

“…This decrease in nitrotyrosine levels is consistent with previous observation of nitrotyrosine clearance from the central nervous system tissue of mice with EAE that are undergoing treatment with UA. 10 In addition, we detected evidence of increased Th2 activity in the peripheral blood of this individual that has previously been reported as beneficial in patients with MS. 29 Mechanistically, the principal therapeutic effects of inosine treatment are likely through raising serum UA levels, thereby reducing the pathological effects of peroxynitritedependent radicals. Radical-mediated oxidative stress may lead to the neuronal and oligodendrocyte loss that underlies the degenerative component of MS.…”

Inhibition of Th17 Cells Regulates Autoimmune Diabetes in NOD Mice

“…Conversely, induction of Th2 populations, which are associated with the transcription factor GATA-3 and cytokines such as IL-4 and -10, results in a dominant protective effect against autoimmunity in this model ( 1 ). This paradigm is not specific to type 1 diabetes; in fact, the relative pathogenic contributions of Th1 cells and protective effects of Th2 cells have been described as a common feature of other organ-specific autoimmune diseases, including multiple sclerosis and rheumatoid arthritis ( 2 – 4 ).…”