To investigate the therapeutic potential of immunochemotherapy with cisplatin + 78 kDa + MPL‐A against Leishmania donovani in BALB/c mice

Abstract

Leishmaniasis has recently garnered attention as one of the diseases 'most neglected' by drug research and development, as the current therapeutic modalities available for the patients are ridden with unacceptable toxicity due to high dosage of the drug, prolonged treatment schedules, resistance and prohibitive costs. A successful chemotherapy requires a restoration of immune response; therefore, we combined Leishmania-specific 78 kDa antigen (with or without adjuvant MPL-A) along with a novel drug cisplatin in infected BALB/c mice and did its comparative analysis with chemotherapy and immunotherapy alone. Animals that were treated with immunochemotherapy showed maximum curative potential as demonstrated by a marked reduction in parasite load. Delayed-type hypersensitivity response to leishmanial antigens has been widely used to assess the level of host protection to the disease. An increased delayed-type hypersensitivity (DTH) response was observed in animals given immunotherapy or chemotherapy or immunochemotherapy; however, maximum DTH response was observed in animals treated with cisplatin + 78 kDa + MPL-A. These animals were also found to exhibit higher IgG2a levels greater cytokine (IFN-γ and IL-2) concentrations suggesting the generation of a strong Th1 type of immune response which is responsible for resolution of the disease.

A Chimera of Th1 Stimulatory Proteins of Leishmania donovani Offers Moderate Immunotherapeutic Efficacy with a Th1-Inclined Immune Response against Visceral Leishmaniasis

“…In addition, an elevated IFN-γ/IL-10 ratio in response to the chimeric protein treatment reflects the Th1-driven immune polarization in corroboration with the above findings [54]. On the contrary, Th2 cytokines, TGF-β and IL-4, which play a critical role in parasite survival, disease progression, and suppression of Th1-associated cure of murine VL [52,55] were decreased in rLdT-E/BCG-treated animals' splenic tissues, and a noticeable decrease in the immunosuppressive cytokine, IL-10, was also observed in sera of treated animals. .…”

Immunogenicity and efficacy of recombinant 78 kDa antigen of Leishmania donovani formulated in various adjuvants against murine visceral leishmaniasis

“…The L. donovani strain was maintained by serial subcultures in the same medium after every 48-72 h [15].…”

Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis

“…This study corroborates well with those that have reported failure of induction of cellular immunity in Leishmania-infected animals contributing to the disease exacerbation. 46,47 lymphoproliferation and cytokine analysis Splenocytes of animals treated with NLA proliferated upon in vitro recall with SLA, whereas no such proliferation was seen in infected control or animals treated with free artemisinin and empty nanoparticles. AmB-treated animals showed the highest rate of proliferation of splenocytes ( Figure 5B and S2).…”