Anti-inflammatory effect of a retrovirus-derived immunosuppressive peptide in mouse models
- Equal contributors
1 Department of Infectious Diseases, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus, Denmark
2 Department of Dermatology, Aarhus University Hospital, 8000 Aarhus, Denmark
3 Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus, Denmark
4 SKAU Vaccines Aps, Åbogade 15, 8200 Aarhus, Denmark
BMC Immunology 2013, 14:51 doi:10.1186/1471-2172-14-51Published: 18 November 2013
Short 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.
The 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.
Using 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.