Serum levels of inflammatory cytokines in Rift Valley fever patients are indicative of severe disease
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Date
Authors
Jansen van Vuuren, Petrus
Shalekoff, Sharon
Grobbelaar, Antoinette A.
Archer, Brett N.
Thomas, Juno
Tiemessen, Caroline T.
Paweska, Janusz Tadeusz
Journal Title
Journal ISSN
Volume Title
Publisher
BioMed Central
Abstract
BACKGROUND : Rift Valley fever (RVF) is a mosquito-borne viral zoonosis affecting domestic and wild ruminants,
camels and humans. Outbreaks of RVF are characterized by a sudden onset of abortions and high mortality
amongst domestic ruminants. Humans develop disease ranging from a mild flu-like illness to more severe
complications including hemorrhagic syndrome, ocular and neurological lesions and death. During the RVF
outbreak in South Africa in 2010/11, a total of 278 human cases were laboratory confirmed, including 25 deaths.
The role of the host inflammatory response to RVF pathogenesis is not completely understood.
METHODS : Virus load in serum from human fatal and non-fatal cases was determined by standard tissue culture
infective dose 50 (TCID50) titration on Vero cells. Patient serum concentration of chemokines and cytokines involved
in inflammatory responses (IL-8, RANTES, CXCL9, MCP-1, IP-10, IL-1β, IL-6, IL-10, TNF and IL-12p70) was determined
using cytometric bead assays and flow cytometry.
RESULTS : Fatal cases had a 1-log10 higher TCID50/ml serum concentration of RVF virus (RVFV) than survivors (p < 0.05).
There were no significant sequence differences between isolates recovered from fatal and non-fatal cases. Chemokines
and pro- and anti-inflammatory cytokines were detected at significantly increased (IL-8, CXCL9, MCP-1, IP-10, IL-10) or
decreased (RANTES) levels when comparing fatal cases to infected survivors and uninfected controls, or when
comparing combined infected patients to uninfected controls.
CONCLUSIONS : The results suggest that regulation of the host inflammatory responses plays an important role in the
outcome of RVFV infection in humans. Dysregulation of the inflammatory response contributes to a fatal outcome. The
cytokines and chemokines identified in this study that correlate with fatal outcomes warrant further investigation as
markers for disease severity.
Description
Keywords
Inflammation, Pathogenesis, Rift Valley fever (RVF)
Sustainable Development Goals
Citation
Jansen van Vuren, P, Shalekoff, S, Grobbelaar, AA, Archer, BN, Thomas, J, Tiemessen, CT & Paweska, JT 2015, 'Serum levels of inflammatory cytokines in Rift Valley fever patients are indicative of severe disease', Virology Journal, vol. 12, art. #159, pp. 1-14.