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Cutting Edge: Inhibition of IL-6 Trans-Signaling Protects from Malaria-Induced Lethality in Mice
Journal article   Peer reviewed

Cutting Edge: Inhibition of IL-6 Trans-Signaling Protects from Malaria-Induced Lethality in Mice

Claudia M. Wunderlich, Denis Delic, Kristina Behnke, Andreas Meryk, Peter Stroehle, Bhagirath Chaurasia, Saleh Al-Quraishy, Frank Wunderlich, Jens C. Bruening and F. Thomas Wunderlich
The Journal of immunology (1950), Vol.188(9), pp.4141-4144
05/01/2012
DOI: 10.4049/jimmunol.1102137
PMID: 22467660

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Abstract

Circulating IL-6 levels correlate with the severity of blood-stage malaria in humans and mouse models, but the impact of IL-6 classic signaling through membrane IL-6R alpha, as well as IL-6 trans-signaling through soluble IL-6R alpha, on the outcome of malaria has remained unknown. In this study, we created IL-6R alpha-deficient mice that exhibit a 50% survival of otherwise lethal blood-stage malaria of the genus Plasmodium chabaudi. Inducing IL-6 trans-signaling by injection of mouse recombinant soluble IL-6R alpha in IL-6R alpha-deficient mice restores the lethal outcome to malaria infection. In contrast, inhibition of IL-6 trans-signaling via injection of recombinant sGP130Fc protein in control mice results in a 40% survival rate. Our data demonstrate that IL-6 trans-signaling, rather than classic IL-6 signaling, contributes to malaria-induced lethality in mice, preceded by an increased inflammatory response. Therefore, inhibition of IL-6 trans-signaling may serve as a novel promising therapeutic basis to combat malaria. The Journal of Immunology, 2012, 188: 4141-4144.
Immunology Life Sciences & Biomedicine Science & Technology

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