Skip to main content

Advertisement

Log in

Evaluation of the alum–naloxone adjuvant activity against experimental murine leishmaniasis due to L. major

  • Review Article
  • Published:
Journal of Parasitic Diseases Aims and scope Submit manuscript

Abstract

Leishmaniasis is caused by intracellular parasites of Leishmania species, which are transmitted by the bite of the sandfly. Recovery and protection against the infection depends on the induction of a strong Th1 type of immune response. Vaccination of mice with the opioid antagonist naloxone can promote the activation of the Th1 responses. We studied the efficacy of the mixture of naloxone and alum, as an adjuvant, to enhance immune responses and induce protection against Leishmania major infection in BALB/c as a susceptible mouse model. BALB/c mice were immunized with Ag–naloxone–alum, Ag–alum, Ag–naloxone or PBS subcutaneously three times at 2-week intervals. The humoral and cellular specific immune responses were assessed 2 weeks after the last immunization and compared with the control mice. Our results indicated that the administration of alum–naloxone as an adjuvant increased the capability of L. major promastigote antigens to enhance lymphocyte proliferation, the levels of IFN-γ, and the IFN-γ/IL-5 ratio. The results of DTH showed that there were no significant differences in footpad swelling between the groups of immunized mice as compared with the non-vaccinated control group; however, no significant differences were observed in the survival rate among groups. It can be concluded that although immunization with the alum–naloxone mixture in combination with the autoclaved L. major promastigote antigens could enhance cellular immunity and shift the immune response to a Th1 pattern, it could not protect the mice against Leishmania major infection.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Ameen M (2010) Cutaneous leishmaniasis: advances in disease pathogenesis, diagnostics and therapeutics. Clin Exp Dermatol 35(7):699–705

    Article  CAS  PubMed  Google Scholar 

  • Badiee A, Jaafari MR, Khamesipour A (2007) Leishmania major: immune response in BALB/c mice immunized with stress-inducible protein 1 encapsulated in liposomes. Exp Parasitol 115(2):127–134

    Article  CAS  PubMed  Google Scholar 

  • Ebrahimpour S, Tabari MA, Youssefi MR, Aghajanzadeh H, Behzadi MY (2013) Synergistic effect of aged garlic extract and naltrexone on improving immune responses to experimentally induced fibrosarcoma tumor in BALB/c mice. Pharmacogn Res 5(3):189–194

    Article  CAS  Google Scholar 

  • Friedman H, Newton C, Klein TW (2003) Microbial infections, immunomodulation, and drugs of abuse. Clin Microbiol Rev 16(2):209–219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jamali A, Mahdavi M, Shahabi S, Hassan ZM, Sabahi F, Javan M (2007) Naloxone, an opioid receptor antagonist, enhances induction of protective immunity against HSV-1 infection in BALB/c mice. Microb Pathog 43(5–6):217–223

    Article  CAS  PubMed  Google Scholar 

  • Jazani NH, Karimzad M, Mazloomi E, Sohrabpour M, Hassan ZM, Ghasemnejad H (2010) Evaluation of the adjuvant activity of naloxone, an opioid receptor antagonist, in combination with heat-killed Listeria monocytogenes vaccine. Microbes Infect 12(5):382–388

    Article  CAS  PubMed  Google Scholar 

  • Jazani NH, Parsania S, Sohrabpour M, Mazloomi E, Karimzad M, Shahabi S (2011) Naloxone and alum synergistically augment adjuvant activities of each other in a mouse vaccine model of Salmonella typhimurium infection. Immunobiology 216(6):744–751

    Article  CAS  PubMed  Google Scholar 

  • Karaji AG, Hamzavi Y (2012) The opioid antagonist naloxone inhibits Leishmania major infection in BALB/c mice. Exp Parasitol 130(1):73–77

    Article  CAS  PubMed  Google Scholar 

  • Manfredi B, Sacerdote P, Bianchi M, Locatelli L, Veljic-Radulovic J, Panerai AE (1993) Evidence for an opioid inhibitory effect on T cell proliferation. J Neuroimmunol 44(1):43–48

    Article  CAS  PubMed  Google Scholar 

  • McCarthy L, Wetzel M, Sliker JK, Eisenstein TK, Rogers TJ (2001) Opioids, opioid receptors and the immune response. Drug Alcohol Depend 62(2):111–123

    Article  CAS  PubMed  Google Scholar 

  • Mohammadzadeh Hajipirloo H, Bozorgomid A, Shahabi S, Hazrati Tappeh K, Karamati SA (2014) Evaluation of alum–naltrexone adjuvant activity, on efficacy of anti-leishmania immunization with autoclaved leishmania major (MRHO/IR/75/ER) antigens in BALB/C mice. Iran J Parasitol 9(3):311–318

    PubMed  PubMed Central  Google Scholar 

  • Molla Hassan AT, Hassan ZM, Moazzeni SM, Mostafaie A, Shahabi S, Ebtekar M (2009) Naloxone can improve the anti-tumor immunity by reducing the CD4+ CD25+ Foxp3+ regulatory T cells in BALB/c mice. Int Immunopharmacol 9(12):1381–1386

    Article  CAS  PubMed  Google Scholar 

  • Nagill R, Kaur S (2011) Vaccine candidates for leishmaniasis: a review. Int Immunopharmacol 11(10):1464–1488

    Article  CAS  PubMed  Google Scholar 

  • Panerai AE, Manfredi B, Granucci F, Sacerdote P (1995) The beta-endorphin inhibition of mitogen-induced splenocytes proliferation is mediated by central and peripheral paracrine/autocrine effects of the opioid. J Neuroimmunol 58(1):71–76

    Article  CAS  PubMed  Google Scholar 

  • Roy S, Ninkovic J, Banerjee S, Charboneau RG, Das S, Dutta R, Kirchner VA (2011) Opioid drug abuse and modulation of immune function: consequences in the susceptibility to opportunistic infections. J Neuroimmune Pharmacol 6(4):442–465

    Article  PubMed  PubMed Central  Google Scholar 

  • Sacerdote P, Bianchi M, Panerai AE (1996) Involvement of beta-endorphin in the modulation of paw inflammatory edema in the rat. Regul Pept 63(2–3):79–83

    Article  CAS  PubMed  Google Scholar 

  • Sacerdote P, di San Secondo VE, Sirchia G, Manfredi B, Panerai AE (1998) Endogenous opioids modulate allograft rejection time in mice: possible relation with Th1/Th2 cytokines. Clin Exp Immunol 113(3):465–469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sacerdote P, Gaspani L, Panerai AE (2000) The opioid antagonist naloxone induces a shift from type 2 to type 1 cytokine pattern in normal and skin-grafted mice. Ann N Y Acad Sci 917:755–763

    Article  CAS  PubMed  Google Scholar 

  • Shahabi S, Mohammadzadeh Hajipirloo H, Keramati A, Hazrati Tappeh K, Bozorgomid A (2014) Evaluation of the adjuvant activity of propranolol, a beta-adrenergic receptor antagonist, on efficacy of a malaria vaccine model in BALB/c mice. Iran J Allergy Asthma Immunol 13(5):307–316

    PubMed  Google Scholar 

  • Singh B, Sundar S (2012) Leishmaniasis: vaccine candidates and perspectives. Vaccine 30(26):3834–3842

    Article  CAS  PubMed  Google Scholar 

  • Sukumaran B, Madhubala R (2004) Leishmaniasis: current status of vaccine development. Curr Mol Med 4(6):667–679

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to acknowledge the grammatical revision of the manuscript in English facilitated by the Consultation Unit, Office of Publications and Scientometrics, Tehran University of Medical Sciences.

Funding

This study was supported by Urmia University of Medical Sciences, Urmia, Iran (Grant No. 753).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Arezoo Bozorgomid.

Ethics declarations

Conflict of interest

We declare that we have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bozorgomid, A., Hajipirloo, H.M., Tappeh, K.H. et al. Evaluation of the alum–naloxone adjuvant activity against experimental murine leishmaniasis due to L. major . J Parasit Dis 40, 1141–1145 (2016). https://doi.org/10.1007/s12639-015-0731-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12639-015-0731-8

Keywords

Navigation