Skip to main content
Top
Published in: Journal of Parasitic Diseases 4/2016

01-12-2016 | Review Article

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

Authors: Arezoo Bozorgomid, Habib Mohammadzadeh Hajipirloo, Khosrow Hazrati Tappeh, Naser Nazari, Seyed Ahmad Karamati, Samira Shirooie

Published in: Journal of Parasitic Diseases | Issue 4/2016

Login to get access

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.
Literature
go back to reference Ameen M (2010) Cutaneous leishmaniasis: advances in disease pathogenesis, diagnostics and therapeutics. Clin Exp Dermatol 35(7):699–705CrossRefPubMed Ameen M (2010) Cutaneous leishmaniasis: advances in disease pathogenesis, diagnostics and therapeutics. Clin Exp Dermatol 35(7):699–705CrossRefPubMed
go back to reference 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):127–134CrossRefPubMed 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):127–134CrossRefPubMed
go back to reference 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):189–194CrossRef 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):189–194CrossRef
go back to reference 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):217–223CrossRefPubMed 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):217–223CrossRefPubMed
go back to reference 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):382–388CrossRefPubMed 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):382–388CrossRefPubMed
go back to reference 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):744–751CrossRefPubMed 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):744–751CrossRefPubMed
go back to reference Karaji AG, Hamzavi Y (2012) The opioid antagonist naloxone inhibits Leishmania major infection in BALB/c mice. Exp Parasitol 130(1):73–77CrossRefPubMed Karaji AG, Hamzavi Y (2012) The opioid antagonist naloxone inhibits Leishmania major infection in BALB/c mice. Exp Parasitol 130(1):73–77CrossRefPubMed
go back to reference 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):43–48CrossRefPubMed 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):43–48CrossRefPubMed
go back to reference McCarthy L, Wetzel M, Sliker JK, Eisenstein TK, Rogers TJ (2001) Opioids, opioid receptors and the immune response. Drug Alcohol Depend 62(2):111–123CrossRefPubMed McCarthy L, Wetzel M, Sliker JK, Eisenstein TK, Rogers TJ (2001) Opioids, opioid receptors and the immune response. Drug Alcohol Depend 62(2):111–123CrossRefPubMed
go back to reference 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):311–318PubMedPubMedCentral 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):311–318PubMedPubMedCentral
go back to reference 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):1381–1386CrossRefPubMed 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):1381–1386CrossRefPubMed
go back to reference Nagill R, Kaur S (2011) Vaccine candidates for leishmaniasis: a review. Int Immunopharmacol 11(10):1464–1488CrossRefPubMed Nagill R, Kaur S (2011) Vaccine candidates for leishmaniasis: a review. Int Immunopharmacol 11(10):1464–1488CrossRefPubMed
go back to reference 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):71–76CrossRefPubMed 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):71–76CrossRefPubMed
go back to reference 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):442–465CrossRefPubMedPubMedCentral 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):442–465CrossRefPubMedPubMedCentral
go back to reference 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):79–83CrossRefPubMed 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):79–83CrossRefPubMed
go back to reference 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):465–469CrossRefPubMedPubMedCentral 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):465–469CrossRefPubMedPubMedCentral
go back to reference 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 917:755–763CrossRefPubMed 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 917:755–763CrossRefPubMed
go back to reference 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):307–316PubMed 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):307–316PubMed
go back to reference Singh B, Sundar S (2012) Leishmaniasis: vaccine candidates and perspectives. Vaccine 30(26):3834–3842CrossRefPubMed Singh B, Sundar S (2012) Leishmaniasis: vaccine candidates and perspectives. Vaccine 30(26):3834–3842CrossRefPubMed
go back to reference Sukumaran B, Madhubala R (2004) Leishmaniasis: current status of vaccine development. Curr Mol Med 4(6):667–679CrossRefPubMed Sukumaran B, Madhubala R (2004) Leishmaniasis: current status of vaccine development. Curr Mol Med 4(6):667–679CrossRefPubMed
Metadata
Title
Evaluation of the alum–naloxone adjuvant activity against experimental murine leishmaniasis due to L. major
Authors
Arezoo Bozorgomid
Habib Mohammadzadeh Hajipirloo
Khosrow Hazrati Tappeh
Naser Nazari
Seyed Ahmad Karamati
Samira Shirooie
Publication date
01-12-2016
Publisher
Springer India
Published in
Journal of Parasitic Diseases / Issue 4/2016
Print ISSN: 0971-7196
Electronic ISSN: 0975-0703
DOI
https://doi.org/10.1007/s12639-015-0731-8

Other articles of this Issue 4/2016

Journal of Parasitic Diseases 4/2016 Go to the issue