Assessment of the Effects of a Novel Herbal Immunomodulator Drug (IMOD) on Cytokine Profiles in Experimental Canine Visceral Leishmaniasis: a Preliminary Survey.
AbstractBackground: Cytokines play a fundamental role in the regulation of immune responses in remission and/or relapsing of leishmaniasis. Therefore, immunotherapy for the treatment of canine visceral leishmaniasis (CVL) has represented a principle approach in control of the infection. The present research aimed to evaluating the immunotherapeutic potential of a novel herbal immunomodulator drug (IMOD) on CVL.Methods: Twelve mongrel dogs were intravenously infected with Iranian strain of L. infantum and randomly divided into three groups; 1: negative control (non-infected), 2: immunotherapy with IMOD and 3: positive control (non-treated). Cell proliferation and Th1-/Th2-type cytokines were measured in peripheral blood mononuclear cell (PBMC) by cell proliferation kit I (MTT) and enzyme-linked immunospot (ELISpot) assays, respectively.Results : At the 60 days follow-up assessment, no adverse effects were observed in treated interventional group. Cellular proliferation assay indicated that PBMCs of IMOD group had higher stimulation index (SI) than positive control group (p <0.05). Enhancement of CD4+ T cells such as IL-2, IL-4 & IL-10 were detected in negative control group due to in vitro IMOD stimulation 30 days post-treatment. In accordance to decreasing trends of Th1 & Th2 cytokines in positive control group, the mean number of IFN-γ, IL-2, IL-4 and IL-10 spot forming cells (SFCs) down regulated for IMOD group during the study.Conclusion: These data indicate that IMOD had immunomodulatory potential but is not sufficient for total parasitic cure due to balance of Th1/Th2 cytokines. This is a preliminary study and we propose to undertake a series of experiments to evaluate the CVL due to in vitro modulatory effects of IMOD.
Holzmuller P, Cavaleyra M, Moreaux J, Kovacic R, Vincendeau P, Papierok G, et al. Lymphocytes of dogs immunized with purified excreted-secreted antigens of Leishmania infantum co-incubated with Leishmania infected macrophages produce IFN gamma resulting in nitric oxide-mediated amastigote apoptosis. Vet Immunol Immunopathol. 2005; 106:247-57.
Mohebali M, Edrissian GH, Shirzadi MR, Akhoundi B, Hajjaran H, Zarei Z, et al. An observationalstudy on the current distribution of visceral leishmaniasis in different geographical zones of Iran and implication to health policy. Travel Med Infect Dis. 2011; 9: 67-74.
Mohebali M, Taran M, Zarei Z. Rapid detection of Leishmania infantum infection in dogs: comparative study using an immunochromatographic dipstick rK39 test and direct agglutination. Vet Parasitol. 2004; 12: 239-45.
Solano Gallego L, Miró G, Koutinas A, Cardoso L, Grazia Pennisi M, et al. Leish-Vet guidelines for the practical management of canine leishmaniasis. Parasites & Vectors. 2011; 4: 86.
Thakur CP, Kanyok TP, Pandey AK, Sinha GP, Zaniewski AE, et al. A prospective randomized, comparative, open-label trial of the safety and efficacy of paromomycin (aminosidine) plus sodium stibogluconate versus sodium stibogluconate alone for the treatment of visceral leishmaniasis. Tran R Soc Trop Med Hyg. 2000; 94:429-31.
Gomez Ochoa P, Castillo JA, Gascon M, Zarate JJ, Alvarez F, et al. Use of domperidone in the treatment of canine visceral leishmaniasis: A clinical trial. Vet J. 2009; 179: 259-63.
Nakhaee A, Taheri T, Taghikhani M, Mohebali M, Salmanian AH, Fasel N, Rafati S. Humoral and cellular immune responses against Type I cysteine proteinase of Leishmania infantum are higher in asymptomatic than symptomatic dogs selected from a naturally infected population. Vet Parasitol. 2004; 119:107-23.
Noazin S, Khamesipour A, Moulton LH, Tanner M, et al. Efficacy of killed whole-parasite vaccines in the prevention of leishmaniasis—A meta-analysis. Vaccine. 2009; 27:4747-53.
Borja Cabrera GP, Mendes AC, Paraguai de Souza E, Lilian Y, Okada H, et al. Effective immunotherapy against canine visceral leishmaniasis with the FML-vaccine. Vaccine. 2004; 22:2234-43.
Guarga JL, Moreno J, Lucientes J, Jesu´s Gracia M, Periba´n˜ez MA, et al. Evaluation of a specific immunochemotherapy for the treatment of canine visceral leishmaniasis. Vet Immunol Immunopathol. 2002; 88:13-20.
Miret J, Nascimento E, Sampaio W, Franc JC, et al. Evaluation of an immunochemotherapeutic protocol constituted of N-methyl meglumine antimoniate (Glucantime®) and the recombinant Leish-110f® + MPL-SE® vaccine to treat canine visceral leishmaniasis. Vaccine. 2008; 26:1585-94.
Gradoni L. An update on antileishmanial vaccine candidates and prospects for a canine Leishmania vaccine. Vet Parasitol. 2001; 100:87-103.
Martino RF, Davicino RC, Mattar MA, Casali YA, Correa SG, Anesini C, Micalizzi B. In vitro immunomodulatory effects of fractions obtained from aqueous extracts of Larrea divaricata Cav (Jarilla) on mouse peritoneal macrophages. Immunopharmacol Immunotoxicol. 2010; 32(1):125-32.
Wang RR, Gu Q, Yang LM, Chen JJ, Li SY, Zheng YT, Anti-HIV-1 activities of extracts from the medicinal plant Rhus chinensis. J Ethnopharmacol. 2006; 105(1-2):269-73.
Tiuman TS, Santos AO, Tania Ueda-Nakamura T, Dias Filho BP, Nakamura CV. Recent advances in leishmaniasis treatment. Inter J Infec Dis. 2011; 1:525-32.
Vila-Nova NS, Maia de Morais S, Cajazeiras Falc MJ, Negreiros Alcantara TT, Travassos Ferreira PA, et al. Different susceptibilities ofm Leishmania spp. promastigotes to the Annona muricata acetogenins annonacinone and corossolone, and the Platymiscium floribundum coumarin scoparone. Exp Parasitol. 2013; 133:334-8.
Golsaz Shirazi F, Raoufi A, Yousefi M, Asgarian Omran H, Memarian A, Khoshnoodi J, et al. In vitro immunoinhibitory effects of Setarud on human B lymphocyte. J Med Plants Res. 2011; 5(11): 2223-31.
Mohseni Salehi Monfared SS, Habibollahzadeh E, Sadeghi H, Maryam Baeeri M, Abdollahi M. Efficacy of Setarud (IMOD), a novel electromagnetically- treated multi-herbal compound, in mouse immunogenic type-1 diabetes. Arch Med Sci. 2010;5:663-9.
Novitsky YA, Madani H, Gharibdoust F, FarhadiM, Farzamfar B, Mohraz M. European patent application. 2007; EP Patent No. EP 2 087 825 A3. Available from: http://www.wipo.int/pctdb/en/wo.jsp?wo=2007087825&IA=WO2007087825&DISPLAY=DESC.
Mohammdirad A, Khorram Khorshid HR, Gharibdoust F, Abdollahi M. Seatrud (IMOD) as a multiherbal drug with promising benefits in animal and human studies: A comprehensive review of biochemical and cellular evidences. Asian J Anim Vet Adv. 2011; 6(12):1185-92.
Rezvanfar MA, Ahmadi A, Shojaei Saadid HA,n Baeeria M, Abdollahi M. Molecular mechanisms of a novel selenium-based complementary medicine which confers protection against hyperandrogenism-induced polycystic ovary. Theriogenology. 2012; 78:620-31.
Carrillo E, Ahmed S, Goldsmith Pestana K, Nieto J, Osorio Y, Travi B, et al. Immunogen-icity of the P-8 amastigote antigen in the experimental model of canine visceral leishmaniasis. Vaccine. 2007; 25:1534-43.
Barbosa Reis A, Martins Filho OA, Teixeira Carvalho A, Giunchetti RC, et al. Systemic and compartmentalized immune response in canine visceral Leishmaniasis. Vet Immunol Immunopathol. 2009; 128:87-95.
Mohebali M, Hajjaran H, Hamzavi Y, Mobedi I, Arshi Sh, Zarei Z, et al. Epidemiological aspects of canine visceral leishmaniasis in the Islamic Republic of Iran. Vet Parasitol. 2005; 129:243-51.
Jamshidi Sh, Avizeh R, Mohebali M, Bokaie S. Immunotherapy using autoclaved L. major antigens and M. vaccae with meglumine antimoniate, for the treatment of experimental canine visceral leishmaniasis Iran J Parasitol. 2011; 6(2):26-34.
Gomes YM, Paiva Cavalcanti M, Lira RA, Abath FGC, Alves LC. Diagnosis of canine visceral leishmaniasis: Biotechnological advances. Vet J. 2008; 175:45-52.
Trigo J, Abbehusen M, Netto EM, Nakatani M, Pedral-Sampaio G, et al. Treatment of canine visceral leishmaniasis by the vaccine Leish-111f + MPL-SE. Vaccine. 2010; 28:3333-40.
Carrillo E, Moreno J. Cytokine profiles in canine visceral leishmaniasis. Vet Immunol Immunopathol. 2009; 128: 67-70.
Moreno J, Alvar J. Canine leishmaniasis: epidemiological risk and the experimental model. Trends Parasitol. 2002; 18: 399-405.
Dı´az I, Mateu E. Use of ELISPOT and ELISA to evaluate IFN-γ, IL-10 and IL-4 responses in conventional pigs. Vet Immunol Immunopathol. 2005; 106:107-112.
Karlsson AC, Martin JN, Younger SR, Bredt BM, Lorrie Epling L, Rollie Ronquillo R, et al. Comparison of the ELISPOT and cytokine flow cytometry assays for the enumeration of antigen-specific T cells. J Immunol Methods. 2003; 283:141-53.
Tassignon J, Burny W, Samira Dahmani S, Zhou L, Stordeur P, Byl B, et al. Monitoring of cellular responses after vaccination against tetanus toxoid: Comparison of the measurement of IFN-g production by ELISA, ELISPOT, flow cytometry and real-time PCR. J Immunol Methods. 2005; 305:188-98.
Ryan C, Gigue`re S, Hagen J, Hartnett C, Kalyuzhny AE. Effect of age and mitogen on the frequency of interleukin-4 and interferon gamma secreting cells in foals and adult horses as assessed by an equine-specific ELISPOT assay. Vet Immunol Immunopathol. 2010; 133: 66-71.
Rodrı´guez-Corte´s A, Ojeda A, Lo´pez Fuertes L, Timo´n M, Laura Altet L, et al. A long term experimental study of canine visceral leishmaniasis. Int J Parasitol. 2007; 37:683-93.
Pinelli E, Van der Kaaij SY, Slappendel R, Fragio C, Ruitenberg EJ, Bernadina W, et al. Detection of canine cytokine gene expression by reverse transcription-polymerase chain reaction. Vet Immunol Immunopathol. 1999; 69:121-26.
Reis AB, Martins-Filho OA, Teixeira Carvalho A, Carvalho MG, Mayrink W, Franca Silva JC, et al. Parasite density and impaired biochemical/ hematological status are associated with severeclinical aspects of canine visceral leishmaniasis.Res Vet Sci. 2006; 81:68-75.
Nagill R, Mahajan R, Sharma M, Kaur S. Induction of cellular and humoral responses by autoclaved and heat-killed antigen of Leishmania donovani in experimental visceral leishmaniasis. Parasitol Int. 2009; 58:359-66.
Hasani-Ranjbar S, Larijani B, Abdollahi M.A systematic review of Iranian medicinal plants useful in diabetes mellitus. Arch Med Sci. 2008; 4:285-92.