Determination of Toll-Like Receptor-Induced Cytokine Profiles in the Blood and Cerebrospinal Fluid of Chikungunya Patients

Abstract

Background: Chikungunya infection caused by Chikungunya virus (CHIKV) is an inflammatory disease affecting the joints and may also lead to neurological complications. We investigated a panel of human Toll-like receptor (TLR)-induced cytokines in Chikungunya patients with and without neurological complications. Methods: In a case-control study, a panel of 12 cytokines and chemokines, TNF-α, IFN-α, IL-1β, IL-6, IL-12, IL-17A, IL-8, monocyte chemotactic protein (MCP)-1, RANTES, interferon (IFN)-γ-induced protein (IP)-10, monokine induced by IFN-γ (MIG) and thymus and activation-regulated chemokine (TARC), was analysed using a conventional ELISA protocol in the serum samples of Chikungunya patients without neurological complications and in the cerebrospinal fluid (CSF) and paired serum samples of Chikungunya patients with neurological complications. Results: The levels of 3 cytokines, IL-1β, IL-17A and IL-8, and 4 chemokines, MCP-1, RANTES, IP-10 and TARC, were raised in serum samples of Chikungunya patients without neurological complications, whereas, 4 cytokines, TNF-α, IFN-α, IL-6 and IL-8, and 4 chemokines, MCP-1, RANTES, MIG and TARC, were elevated in CSF samples of Chikungunya patients with neurological complications. Moreover, the levels of IL-6 and IL-8 cytokines were significantly elevated in the CSF compared to paired serum samples in Chikungunya patients with neurological complications. Conclusions: In CHIKV infection, multiple cytokines are elevated in serum and CSF. The elevation in IL-6 and IL-8 cytokines in CSF correlates with neurological involvement.

A Systematic Meta-analysis of Immune Signatures in Patients With Acute Chikungunya Virus Infection

“…Of the 14 studies identified, 5 were excluded from the meta-analysis because their data could not be extracted for analysis: in 1 study, the results from the cytokine assay were presented as optical density readings and could not be computed into concentration values [ 26 ]; another study contained data from only a single patient [ 28 ]. To overcome the lack of immune mediator profiles from non-CHIKV controls in this study, we used the data from healthy controls in a previously published study [ 24 ] as a reference to perform the analysis.…”

“…Five of the 14 studies were excluded from the meta-analysis because their data could not be extracted for analysis. In 1 study, data were presented as optical density readings and could not be computed into concentration values [ 26 ]; 1 study contained data from only a single patient [ 28 ]; 2 studies provided only the median or mean of the control group without any estimates of the variance [ 25 , 27 ]; and 1 study provided median values with interquartile ranges for the patient and control groups [ 33 ]. Nevertheless, apart from the single-patient study [ 26 ], fold changes were computed for these studies, and they were depicted in the heat maps but not used in the meta-analysis.…”

The neurological complications of chikungunya virus: A systematic review

“…A study from India compared the cytokine profile for patients with and without neurological complications following chikungunya infection . Of those with neurological disease, 4 had encephalitis and 1 had “neuropathy.” Concentrations of 4 cytokines (TNF‐α, IFN‐α, IL‐6, and monokine induced by IFN‐γ) were found to be significantly higher in patients with neurological disease secondary to chikungunya, as opposed to uncomplicated chikungunya infection.…”

Prevalence of chronic chikungunya and associated risks factors in the French West Indies (La Martinique): A prospective cohort study

“…CHIKV is known to target human epithelial and endothelial cells, fibroblasts and macrophages [13][14][15], as well as human muscle satellite cells [16]. The virus is also suspected of neurotropism [17,18], which can lead to neurological complications [19][20][21][22].…”