Skip to main content
SpringerLink
Log in

Vasoactive Intestinal Polypeptide Suppressed Experimental Autoimmune Encephalomyelitis by Inhibiting T Helper 1 Responses

  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Vasoactive intestinal peptide (VIP) has been found to act as a potent anti-inflammatory factor through regulating the production of both anti- and pro-inflammatory mediators and promoting Th2-type responses. In this study, we used myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice to investigate the potential effects of VIP on multiple sclerosis. Our results showed that in vivo treatment of EAE-induced mice with VIP had great protective benefit at both clinical and histological levels. Disease suppression was associated with the inhibition of T cells proliferation, shifting of the immune response toward a Th2-type response and influencing the expression of pro-inflammatory cytokines including IFN-γ, IL-6 and IL-2 as well as chemotactic factors such as RANTES. In conclusion, the study provides evidence that VIP had great protective effect on EAE through its inhibition actions on pathogenic T cells and through a specific effect on the Th1 response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.

Similar content being viewed by others

REFERENCES

  1. Said SI, Mutt V: Polypeptide with broad biological activity: Isolation from small intestine. Science 169:1217–1218, 1970.

    Article  PubMed  CAS  Google Scholar 

  2. Blalock JE: The syntax of immune-neuroendocrine communication. Immunol Today 15:504–511, 1994.

    Article  PubMed  CAS  Google Scholar 

  3. Gomariz RP, Martinez C, Abad C, Leceta J, Delgado M: Immunology of VIP: A review and therapeutical perspectives. Curr Pharm Des 7:89–111, 2001.

    Article  PubMed  CAS  Google Scholar 

  4. Pozo D: VIP- and PACAP-mediated immunomodulation as prospective therapeutic tools. Trends Mol Med 9:211–217, 2003.

    Article  PubMed  CAS  Google Scholar 

  5. Delgado M, Pozo D, Ganea D: The significance of vasoactive intestinal peptide in immunomodulation. Pharmacol Rev 56:249–290, 2004.

    Article  PubMed  CAS  Google Scholar 

  6. Calvo JR, Pozo D, Guerrero JM: Functional and molecular characterization of VIP receptors and signal transduction in human and rodent immune systems. Adv Neuroimmunol 6:39–47, 1996.

    Article  PubMed  CAS  Google Scholar 

  7. Harmar AJ, Arimura A, Gozes I, Journot L, Laburthe M, Pisegna JR, Rawlings SR, Robberecht P, Said SI, Sreedharan SP, Wank SA, Waschek JA: International Union of Pharmacology. XVIII. Nomenclature of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Pharmacol Rev 50:265–270, 1998.

    PubMed  CAS  Google Scholar 

  8. Delgado M: VIP: A very important peptide in T helper differentiation. Trends Immunol 24:221–224, 2003.

    Article  PubMed  CAS  Google Scholar 

  9. Abad C, Martinez C, Juarranz MG, Arranz A, Leceta J, Delgado M, Gomariz RP: Therapeutic effects of vasoactive intestinal peptide in the trinitrobenzene sulfonic acid mice model of Crohn’s disease. Gastroenterology 124:961–971, 2003.

    Article  PubMed  CAS  Google Scholar 

  10. Keino H, Kezuka T, Takeuchi M, Yamakawa N, Hattori T, Usui M: Prevention of experimental autoimmune uveoretinitis by vasoactive intestinal peptide. Arch Ophthalmol 122:1179–1184, 2004.

    Article  PubMed  CAS  Google Scholar 

  11. Delgado M, Abad C, Martinez C, Leceta J, Gomariz RP: Vasoactive intestinal peptide prevents experimental arthritis by downregulating both autoimmune and inflammatory components of the disease. Nat Med 7:563–568, 2001.

    Article  PubMed  CAS  Google Scholar 

  12. Giovannoni G, Hartung HP: The immunopathogenesis of multiple sclerosis and Guillain-Barre syndrome. Curr Opin Neurol 9:165–177, 1996.

    Article  PubMed  CAS  Google Scholar 

  13. Zamvil SS, Steinman L: The T lymphocyte in experimental allergic encephalomyelitis. Annu Rev Immunol 8:579–621, 1990.

    Article  PubMed  CAS  Google Scholar 

  14. Steinman L: Assessment of animal models for MS and demyelinating disease in the design of rational therapy. Neuron 24:511–514, 1999.

    Article  PubMed  CAS  Google Scholar 

  15. Bernard CC, Johns TG, Slavin A, Ichikawa M, Ewing C, Liu J, Bettadapura J: Myelin oligodendrocyte glycoprotein: A novel candidate autoantigen in multiple sclerosis. J Mol Med 75:77–88, 1997.

    Article  PubMed  CAS  Google Scholar 

  16. Wekerle H, Kojima K, Lannes-Vieira J, Lassmann H, Linington C: Animal models. Ann Neurol 36(Suppl):S47–S53, 1994.

    Article  Google Scholar 

  17. Teresi S, Boudard F, Bastide M: Effect of calcitonin gene-related peptide and vasoactive intestinal peptide on murine CD4 and CD8 T cell proliferation. Immunol Lett 50:105–113, 1996.

    Article  PubMed  CAS  Google Scholar 

  18. Delgado M, Chorny A, Gonzalez-Rey E, Ganea D: Vasoactive intestinal peptide generates CD4+CD25+ regulatory T cells in vivo. J Leukoc Biol 78:1327–1338, 2005.

    Article  PubMed  CAS  Google Scholar 

  19. Ersoy E, Kus CN, Sener U, Coker I, Zorlu Y: The effects of interferon-beta on interleukin-10 in multiple sclerosis patients. Eur J Neurol 12:208–211, 2005.

    Article  PubMed  CAS  Google Scholar 

  20. Youssef S, Stuve O, Patarroyo JC, Ruiz PJ, Radosevich JL, Hur EM, Bravo M, Mitchell DJ, Sobel RA, Steinman L, Zamvil SS: The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 420:78–84, 2002.

    Article  PubMed  CAS  Google Scholar 

  21. Delgado M, Munoz-Elias EJ, Gomariz RP, Ganea D: VIP and PACAP inhibit IL-12 production in LPS-stimulated macrophages. Subsequent effect on IFNgamma synthesis by T cells. J Neuroimmunol 96:167–181, 1999.

    Article  PubMed  CAS  Google Scholar 

  22. Delgado M, Ganea D: Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit interleukin-12 transcription by regulating nuclear factor kappaB and Ets activation. J Biol Chem 274:31930–31940, 1999.

    Article  PubMed  CAS  Google Scholar 

  23. Delgado M, Leceta J, Gomariz RP, Ganea D: Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide stimulate the induction of Th2 responses by up-regulating B7.2 expression. J Immunol 163:3629–3635, 1999.

    PubMed  CAS  Google Scholar 

  24. Ranger AM, Das MP, Kuchroo VK, Glimcher LH: B7-2 (CD86) is essential for the development of IL-4-producing T cells. Int Immunol 8:1549–1560, 1996.

    Article  PubMed  CAS  Google Scholar 

  25. Ganea D, Delgado M: Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as modulators of both innate and adaptive immunity. Crit Rev Oral Biol Med 13:229–237, 2002.

    Article  PubMed  Google Scholar 

  26. Delgado M, Leceta J, Ganea D: Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide promote in vivo generation of memory Th2 cells. FASEB J 16:1844–1846, 2002.

    PubMed  CAS  Google Scholar 

  27. Eugster HP, Frei K, Kopf M, Lassmann H, Fontana A: IL-6-deficient mice resist myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. Eur J Immunol 28:2178–2187, 1998.

    Article  PubMed  CAS  Google Scholar 

  28. Ransohoff RM: The chemokine system in neuroinflammation: An update. J Infect Dis 186(Suppl 2):S152–S156, 2002.

    Article  PubMed  CAS  Google Scholar 

  29. Delgado M, Ganea D: Inhibition of endotoxin-induced macrophage chemokine production by vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide in vitro and in vivo. J Immunol 167:966–975, 2001.

    PubMed  CAS  Google Scholar 

  30. Gonzalez-Rey E, Fernandez-Martin A, Chorny A, Martin J, Pozo D, Ganea D, Delgado M: Therapeutic effect of vasoactive intestinal peptide on experimental autoimmune encephalomyelitis: Down-regulation of inflammatory and autoimmune responses. Am J Pathol 168:1179–1188, 2006.

    Article  PubMed  CAS  Google Scholar 

Download references

ACKNOWLEDGMENTS

The helpful advice of Prof. Jingwu Zang was greatly appreciated. This work was supported in part by Science and Technology Commission of Shanghai Municipality (Project 04DZ14902), Shanghai Rising-Star Program (04QMX1423) and Shanghai Leading Academic Discipline Project (T0206).

Author information

Authors and Affiliations

  1. Shanghai Institute of Immunology, Shanghai Jiao Tong University Medical School, Shanghai, P. R. China

    Haiyan Li, Yunhua Mei, Ying Wang & Lingyun Xu

  2. Institute of Health Sciences, Shanghai Jiao Tong University/Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, P. R. China

    Haiyan Li & Lingyun Xu

  3. Shanghai Institute of Immunology, Shanghai Jiao Tong University Medical School, Building I Room 308, 225 South Chongqing Road, Shanghai, 200025, P. R. China

    Lingyun Xu

Authors
  1. Haiyan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yunhua Mei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lingyun Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lingyun Xu.

Additional information

Haiyan Li and Yunhua Mei contributed equally to this work

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, H., Mei, Y., Wang, Y. et al. Vasoactive Intestinal Polypeptide Suppressed Experimental Autoimmune Encephalomyelitis by Inhibiting T Helper 1 Responses. J Clin Immunol 26, 430–437 (2006). https://doi.org/10.1007/s10875-006-9042-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10875-006-9042-2

KEY WORDS

Search

Navigation