The Potent ITK/BTK Inhibitor Ibrutinib Is Effective for the Treatment of Experimental Visceral Leishmaniasis Caused by Leishmania donovani

The Journal of Infectious Diseases
Sanjay VarikutiAbhay R Satoskar

Abstract

New drugs are needed for leishmaniasis because current treatments such as pentavalent antimonials are toxic and require prolonged administration, leading to poor patient compliance. Ibrutinib is an anticancer drug known to modulate T-helper type 1 (Th1)/Th2 responses and has the potential to regulate immunity against infectious disease. In this study, we evaluated the efficacy of oral ibrutinib as a host-targeted treatment for visceral leishmaniasis (VL) caused by Leishmania donovani using an experimental mouse model. We found that oral ibrutinib was significantly more effective than the pentavalent antimonial sodium stibogluconate (70 mg/kg) for the treatment of VL caused by L. donovani. Ibrutinib treatment increased the number of interleukin 4- and interferon γ-producing natural killer T cells in the liver and spleen and enhanced granuloma formation in the liver. Further, ibrutinib treatment reduced the influx of Ly6Chi inflammatory monocytes, which mediate susceptibility to L. donovani. Finally, ibrutinib treatment was associated with the increased production of the cytokines interferon γ, tumor necrosis factor α, interleukin 4, and interleukin 13 in the liver and spleen, which are associated with protection against L. donov...Continue Reading

References

Sep 1, 1996·The Journal of Experimental Medicine·M KopfW Solbach
Sep 16, 1998·Clinical and Experimental Immunology·P Choi, H Reiser
Mar 22, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·S C SmeltP M Kaye
Oct 26, 2000·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·S SundarH W Murray
Nov 9, 2000·European Journal of Immunology·J AlexanderF Brombacher
Nov 13, 2001·International Journal of Experimental Pathology·H W Murray
Aug 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paul Gadue, Paul L Stein
Feb 22, 2005·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Devki Nandan, Neil E Reiner
Dec 13, 2006·ChemMedChem·Zhengying PanJames T Palmer
Feb 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Martin Felices, Leslie J Berg
May 9, 2008·PLoS Pathogens·Amanda C StanleyChristian R Engwerda
Jan 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maria C Leite-de-MoraesMichel Dy
May 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Martin FelicesLeslie J Berg
Feb 9, 2010·Nature Immunology·Dale I GodfreyAlan G Baxter
Mar 10, 2010·European Journal of Immunology·Eszter DeakDiane McMahon-Pratt
Jan 11, 2012·Proceedings of the National Academy of Sciences of the United States of America·Hannah E CummingsAbhay R Satoskar
Jan 21, 2012·Nature Reviews. Drug Discovery·Charlotte Harrison
Feb 5, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Catherine C YinLeslie J Berg
Feb 19, 2013·Advances in Applied Microbiology·Gaurav GuptaAbhay R Satoskar
Jan 15, 2014·Immunology Letters·Ramona Hurdayal, Frank Brombacher
Jan 28, 2014·PloS One·Joan Ní GabhannCaroline A Jefferies
Dec 4, 2014·MBio·Luiz Gustavo GardinassiIsabel Kinney Ferreira de Miranda Santos
Mar 3, 2015·Proceedings of the National Academy of Sciences of the United States of America·Idit Sagiv-BarfiRonald Levy
May 6, 2016·Frontiers in Immunology·Elisangela Oliveira de FreitasDaniel Ferreira Feijó
Nov 2, 2017·Scientific Reports·Cesar TerrazasAbhay R Satoskar

❮ Previous
Next ❯

Citations

Aug 10, 2019·Journal of Cellular and Molecular Medicine·Bingjue YeMin Zheng
May 5, 2020·Frontiers in Cellular and Infection Microbiology·Nathan RyanSteve Oghumu
May 13, 2020·Drug Development Research·Myla Lôbo de SouzaPedro José Rolim Neto
Apr 21, 2020·Leukemia & Lymphoma·Denise RisnikRomina Gamberale
Aug 10, 2021·IScience·Samuel WeeksMobin Karimi
Sep 18, 2021·Immunology·Charlotte McDonaldEfterpi Kostareli
Oct 17, 2021·Journal of Experimental & Clinical Cancer Research : CR·Carol MorenoMiguel Villanueva

❮ Previous
Next ❯

Related Concepts