Vitamins (A&D) and Isoprenoid (Chenodeoxycholic acid) molecules are accompanied by Th1 immunostimulatory response and therapeutic cure in vivo: possible antileishmanial drugs

• Published in: Scientific reports 2019-06, Vol.9 (1), p.8531-8531, Article 8531
• Main Authors: Gogulamudi, Venkateswara Reddy, Dubey, Mohan Lal, Kaul, Deepak, Hubert, Donfack Jean, Kandimalla, Ramesh, Sehgal, Rakesh
• Format: Article
• Language: English
• Subjects: 13; 13/21; 13/31; 13/51; 14; 14/63; 631/154/555; 631/250/255; 64/60; Adjuvants, Immunologic - pharmacology; Animals; Antiprotozoal Agents - pharmacology; Chenodeoxycholic acid; Chenodeoxycholic Acid - pharmacology; Cholecalciferol - pharmacology; Cytokines - immunology; Humanities and Social Sciences; Immune response; Immunomodulation; Immunostimulation; Immunosuppression; Immunosuppressive agents; Interleukin 1; Interleukin 4; Interleukin 5; Leishmania donovani - immunology; Leishmaniasis, Visceral - drug therapy; Leishmaniasis, Visceral - immunology; Leishmaniasis, Visceral - pathology; Lymphocytes T; Mice; Mice, Inbred BALB C; multidisciplinary; Parasites; Parasitic diseases; Retinoic acid; Science; Science (multidisciplinary); Spleen; Terpenes; Th1 Cells - immunology; Th1 Cells - pathology; Toxicity; Tumor necrosis factor-α; Vector-borne diseases; Visceral leishmaniasis; Vitamin A; Vitamin A - pharmacology; Vitamin D; Vitamin D3; Vitamins; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-44630-4

Investigation of immune modulatory anti-leishmanial molecules is now being strongly encouraged to overcome the immunosuppression manifested during visceral leishmaniasis (VL), resistance, toxicity and high cost associated with conventional therapeutics. In the present study, we explored the protective efficacy of vitamin D 3 , retinoic acid and isoprenoid chenodeoxycholic acid (CDCA) combinations against L . donovani infected BALB/c mice. We also probed the immune modulatory response (Th1 & Th2 cytokines) and infection dynamics following experimental infections with drug treated animals. Our results indicate that Vit.D 3 /RA and CDCA/RA combination treatment led to significant inhibition of parasite load on days 21 and 28 post treatment. Furthermore, there was a marked inhibition of Th2 type immune responses in IL-4, IL-5 and polarization of Th1 biased immunity along with upregulation of IL-1, IFN-γ, and TNF-α levels on day 28 post treatment. In addition, mice treated with Vit.D 3 /RA and CDCA/RA demonstrates here that splenic histological recovery against the virulent challenge of L . donovani by day 28 was comparable to control group. The conclusions derived from this study suggests that a combination of vitamin A, D 3 and isoprenoids may have a potential immunomodulatory therapeutic role against leishmaniasis.