title: Immunoprotective effect of lentinan in combination with miltefosine on Leishmania-infected J-774A.1 macrophages.
abstract: Rejuvenation of deteriorated host immune functions is imperative for successful annihilation of Leishmania parasites. The use of immunomodulatory agents may have several advantages as they conquer immunosuppression and, when given in combination, improve current therapeutic regimens. We herein investigated the immunostimulatory potency of a β-glucan, lentinan either alone or in combination with short dose of standard drug, miltefosine on Leishmania-infected J-774A.1 macrophages. Our study shows that infected macrophages when stimulated with 2.5 μg/mL and above concentrations of lentinan secreted significant amount of host-protective molecules. The in vitro interaction between lentinan and miltefosine showed some synergy (mean sum of fractional inhibitory concentration [mean ∑FIC] 0.87) at IC50 level. Lentinan (2.5 μg/mL) plus low-dose miltefosine (2 μM) displayed heightened level of pro-inflammatory cytokines, IL-12 (13.6-fold) and TNF-α (6.8-fold) along with nitric oxide (7.2-fold higher) when compared with infected control. In combination group, we also observed remarkably (P<.001) suppressed levels of anti-inflammatory cytokines, IL-10 and TGF-β, than that of untreated macrophages. Additionally, in comparison with infected group, we observed significant induction in phagocytic activity of macrophages in combination with treated group. Collectively, these findings emphasize the immunostimulatory effect of lentinan alone and in combination with low dose of miltefosine against Leishmania donovani.
authors.affiliation: Department of Pathology, King George's Medical University, Lucknow, India. rahul_biotech08@yahoo.com.
authors.forename: R
authors.initials: R
authors.lastname: Shivahare
authors.affiliation: Department of Pathology, King George's Medical University, Lucknow, India. aliwahid78@gmail.com.
authors.forename: W
authors.initials: W
authors.lastname: Ali
authors.affiliation: Department of Pathology, King George's Medical University, Lucknow, India.
authors.forename: U S
authors.initials: US
authors.lastname: Singh
authors.affiliation: Department of Pathology, King George's Medical University, Lucknow, India.
authors.forename: S M
authors.initials: SM
authors.lastname: Natu
authors.affiliation: Department of Pharmacology and Therapeutics, King George's Medical University, Lucknow, India.
authors.forename: S
authors.initials: S
authors.lastname: Khattri
authors.affiliation: Division of Parasitology, CSIR- Central Drug Research Institute, Lucknow, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Puri
authors.affiliation: Division of Parasitology, CSIR- Central Drug Research Institute, Lucknow, India.
authors.forename: S
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D007155:Immunologic Factors / Q000494:pharmacology; D007893:Leishmania donovani / Q000187:drug effects / Q000276:immunology*; D007912:Lentinan / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000469:parasitology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D000981:Antiprotozoal Agents; D016207:Cytokines; D007155:Immunologic Factors; D010767:Phosphorylcholine; D009569:Nitric Oxide; D007912:Lentinan; C039128:miltefosine