| First Author | Wunderlich CM | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 9 | Pages | 4141-4 |
| PubMed ID | 22467660 | Mgi Jnum | J:188445 |
| Mgi Id | MGI:5440557 | Doi | 10.4049/jimmunol.1102137 |
| Citation | Wunderlich CM, et al. (2012) Cutting edge: Inhibition of IL-6 trans-signaling protects from malaria-induced lethality in mice. J Immunol 188(9):4141-4 |
| abstractText | 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-6Ralpha, as well as IL-6 trans-signaling through soluble IL-6Ralpha, on the outcome of malaria has remained unknown. In this study, we created IL-6Ralpha-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-6Ralpha in IL-6Ralpha-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. |
