Adjunctive ruxolitinib attenuates inflammation and enhances immunity in volunteers experimentally infected with Plasmodium falciparum
Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Inhibiting the inflammatory response to malaria offers a promising strategy to improve clinical outcomes and overcome immunoregulatory barriers that hinder development of antiparasitic immunity. We conducted a double-blind, randomized, placebo-controlled trial assessing whether ruxolitinib, a Janus-activated kinase (JAK) 1/2 inhibitor, can reduce inflammatory responses and enhance antiparasitic immunity in malaria-naïve volunteers inoculated with blood-stage Plasmodium falciparum . Twenty participants were inoculated and, on day 8, randomized to receive artemether-lumefantrine with either ruxolitinib or placebo. Ninety days later, participants underwent a second inoculation. Ruxolitinib was safe and well tolerated; moreover, it attenuated inflammatory responses to the initial infection, with reduced posttreatment increases in C-reactive protein and markers of disease severity, including angiopoietin-2 and intercellular adhesion molecule-1. Ruxolitinib also enhanced immune memory after the second infection, with elevated human leukocyte antigen–DRA and 4-1BB, consistent with increased T cell activation. These data support the further evaluation of ruxolitinib as an adjunctive treatment to improve clinical outcomes and boost antiparasitic immunity in clinical malaria.
Source: Science Translational Medicine
Authors: Rebecca Webster, Damian A. Oyong, Stacey Llewellyn, Azrin N. Abd-Rahman, Adam J. Potter, Reena Mukhiya, Nischal Sahai, Indika Leelasena, Eniko Ujvary, Sue Mathison, Dean W. Andrew, Luzia Bukali, Fabian de Labastida Rivera, Jessica Engel, Megan S. F. Soon, Teija Frame, Julianne Hamelink, Mayimuna Nalubega, Nicholas L. Dooley, Jessica R. Loughland, Tran Nguyen, Yael Rosenberg-Hasson, Sofia Maysel-Auslender, Natalia Sigal, Kira Foygel, Jeremy Gower, Jenny Peters, Ria Woo, Fiona Amante, Timothy N. C. Wells, Stephan Chalon, Joerg J. Moehrle, James S. McCarthy, Geoffrey W. Birrell, Michael D. Edstein, Michael Leipold, Gerlinde Obermoser, Holden Maecker, Christian R. Engwerda, Bridget E. Barber, Michelle J. Boyle
Institutions: QIMR Berghofer Medical Research Institute, Burnet Institute, The George Institute for Global Health, Griffith University, University of the Sunshine Coast, The University of Queensland, Stanford University, Medicines for Malaria Venture, Swiss Tropical and Public Health Institute, University of Basel, The University of Melbourne, Peter Doherty Institute, Australian Defence Force Malaria and Infectious Disease Institute, Royal Brisbane and Women's Hospital, Menzies School of Health Research
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4416711874