Anti-inflammatory effect of a retrovirus-derived immunosuppressive peptide in mouse models

Abstract

BackgroundShort dimeric or mulitmeric peptides derived from a highly conserved stretch of amino acids from gammaretroviral envelope proteins has been found to have immunosuppressive properties in vitro. Here we test the hypothesis that such immunosuppressive peptides may serve as immunomodulatory reagents for treatment of inflammatory disorders.ResultsThe anti-inflammatory effect of a synthetic retrovirus-derived immunosuppressive peptide of 17 amino acids was tested in two murine skin inflammation models, a TPA-induced acute toxic contact eczema model and an oxazolone-induced allergic contact dermatitis. Overall, mice (n = 24) treated with a topically applied cream containing the dimeric immunosuppressive peptide exhibited a reduction of 28.8% in ear thickness (range 20.1-42.5), whereas the application of a scrambled peptide dimer or a monomer of the immunosuppressive peptide remained without effect (p = 0.028). Furthermore, ear biopsies from mice treated with the dimeric immunosuppressive peptide showed a significant reduction in mRNA of the pro-inflammatory cytokines TNF-α, IL-17C, and IL-6 as well as the chemokine CXCL2 compared to mice treated with control peptides.ConclusionUsing two murine skin inflammation models, we show that an immunosuppressive retroviral peptide is capable of reducing inflammatory disorders. The results indicate that virus-derived immunosuppressive peptides capable of down-regulating several proinflammatory cytokines may represent a novel class of drugs for the treatment of excess inflammation.

Human Endogenous Retroviral Genetic Element With Immunosuppressive Activity in Both Human Autoimmune Diseases and Experimental Arthritis

“…In both experimental and human arthritis, it is well documented that pro-or antiinflammatory cytokines facilitate or inhibit activation of various immune cells and local tissue cells. These findings are consistent with those in a study by Ciancialo et al and others, who reported that the CKS-17 ISU peptide (derived from exogenous murine retroviruses) had an immunosuppressive effect in mouse models of inflammatory peritonitis and disseminated intravascular coagulation, among others (8,11,38). The human origin and the significant antiinflammatory activity of the Env59 ISU peptide present a potential new treatment strategy for autoimmune and inflammatory diseases.…”

“…One way in which the retroviral envelope (Env) proteins can play a role in human biology is through their inherent immunosuppressive activity , localized to a well‐defined and well‐conserved secondary protein structure (the immunosuppressive [ISU] domain) in the retroviral Env protein. Effects of the ISU domain include inhibition of the immune responses of lymphocytes, monocytes, and macrophages and strong effects on the production of proinflammatory cytokines, which are involved in cell‐to‐cell communication during the immune response and play an essential role in autoimmunity.…”

Deriving Immune Modulating Drugs from Viruses—A New Class of Biologics

“…While this review has focused primarily on poxvirus and herpesvirus derived agents, immune-modulating factors from other viruses are only just beginning to be identified and tested in preclinical studies. For example, a synthetic peptide derived from the murine leukemia virus (MLV) retrovirus is reported to suppress inflammatory damage in two models of skin inflammation in mice [194]. Other organisms including other viruses, fungi and parasites such as malaria and insects have proven immune-modulating actions that have not yet been tapped as potential sources for therapeutics.…”

Human Endogenous Retroviruses: Residues of Ancient Times Are Differentially Expressed in Crohn’s Disease

“…Cianciolo et al [20] showed that an octadecapeptide derived from the ISD can inhibit pro-inflammatory cytokines and induces the expression of anti-inflammatory IL-10 in a murine model of peritonitis. Most recently, Tolstrup et al [19] performed a similar study, investigating the effects of a synthetic retroviral ISD peptide in 2 murine skin inflammation models. Topical application of cream containing this ISD peptide resulted in a reduction of pro-inflammatory cytokines like TNF-alpha and IL-6.…”