Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2011 Sep 16;146(6):861-2.
doi: 10.1016/j.cell.2011.08.027.

A new shield for a cytokine storm

Akiko Iwasaki  1 , Ruslan Medzhitov
Affiliations
Comment

A new shield for a cytokine storm

Akiko Iwasaki et al. Cell. .

Abstract

Highly virulent influenza virus infection results in excessive cytokine production, recruitment of leukocytes, and immune-mediated pulmonary injury. Teijaro et al. (2011) now demonstrate that sphingosine-1-phosphate receptor 1 ligands suppress all features of flu-inflicted pathological inflammation and place the endothelium at the center of this regulatory network.

PubMed Disclaimer

Figures

Figure
Figure. Suppression of inflammation by S1P1 agonists
Influenza virus infects the lung epithelial cells and subsequently alveolar macrophages, and other leukocytes. This results in type I IFN, cytokine and chemokine secretion by various cell types both resident and recruited. S1P1 ligands, CYM05442 and RP-002, engage S1P1 on vascular and lymphatic (not shown) endothelial cells and block chemokine secretion from endothelial cells, which in turn block recruitment of leukocytes to the lung. In addition, S1P1 signaling suppresses type I IFN, cytokine and chemokine secretion from other cells, resulting in reduced immunopathology. However, S1P1 agonists do not impair dendritic cell activation, thereby enabling T cell and B cell responses to be initiated in the draining lymph node.
See this image and copyright information in PMC

Comment on

References

    1. Brinkmann V, Billich A, Baumruker T, Heining P, Schmouder R, Francis G, Aradhye S, Burtin P. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov. 2010;9:883–897. - PubMed
    1. Cahalan SM, Gonzalez-Cabrera PJ, Sarkisyan G, Nguyen N, Schaeffer MT, Huang L, Yeager A, Clemons B, Scott F, Rosen H. Actions of a picomolar short-acting S1P agonist in S1P-eGFP knock-in mice. Nat Chem Biol. 2011;7:254–256. - PMC - PubMed
    1. Cyster JG. Chemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs. Annual review of immunology. 2005;23:127–159. - PubMed
    1. Feldmann A, Schafer MK, Garten W, Klenk HD. Targeted infection of endothelial cells by avian influenza virus A/FPV/Rostock/34 (H7N1) in chicken embryos. Journal of virology. 2000;74:8018–8027. - PMC - PubMed
    1. Manicassamy B, Manicassamy S, Belicha-Villanueva A, Pisanelli G, Pulendran B, Garcia-Sastre A. Analysis of in vivo dynamics of influenza virus infection in mice using a GFP reporter virus. Proc Natl Acad Sci U S A. 2010;107:11531–11536. - PMC - PubMed

LinkOut - more resources