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


RESULTS
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.


CONCLUSIONS
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.
Department of Infectious Diseases, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus, Denmark. martol@rm.dk.
Martin
M
Tolstrup
Claus
C
Johansen
Lars
L
Toft
Finn S
FS
Pedersen
Anne
A
Funding
Shervin
S
Bahrami
Lars
L
Iversen
Lars
L
Østergaard
Mogens
M
Duch
D000595:Amino Acid Sequence; D000818:Animals; D054426:Chemokine CXCL2 / Q000235:genetics; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D017453:Dermatitis, Irritant / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D019281:Dimerization; D004195:Disease Models, Animal; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology* / Q000494:pharmacology; D020381:Interleukin-17 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010081:Oxazolone / Q000276:immunology / Q000633:toxicity; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D012190:Retroviridae / Q000737:chemistry / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000276:immunology / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D054426:Chemokine CXCL2; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D015850:Interleukin-6; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D010081:Oxazolone; D013755:Tetradecanoylphorbol Acetate