Inflammatory Cytokine Expression Is Associated with Chikungunya Virus Resolution and Symptom Severity

Abstract

The Chikungunya virus infection zones have now quickly spread from Africa to parts of Asia, North America and Europe. Originally thought to trigger a disease of only mild symptoms, recently Chikungunya virus caused large-scale fatalities and widespread economic loss that was linked to recent virus genetic mutation and evolution. Due to the paucity of information on Chikungunya immunological progression, we investigated the serum levels of 13 cytokines/chemokines during the acute phase of Chikungunya disease and 6- and 12-month post-infection follow-up from patients of the Italian outbreak. We found that CXCL9/MIG, CCL2/MCP-1, IL-6 and CXCL10/IP-10 were significantly raised in the acute phase compared to follow-up samples. Furthermore, IL-1β, TNF-α, Il-12, IL-10, IFN-γ and IL-5 had low initial acute phase levels that significantly increased at later time points. Analysis of symptom severity showed association with CXCL9/MIG, CXCL10/IP-10 and IgG levels. These data give insight into Chikungunya disease establishment and subsequent convalescence, which is imperative to the treatment and containment of this quickly evolving and frequently re-emerging disease.

The Role of Innate versus Adaptive Immune Responses in a Mouse Model of O'Nyong-Nyong Virus Infection

“…[25][26][27][28][29] In humans, overlap has been identified between persistent CHIKV and rheumatoid arthritis; and proinflammatory mediators seem to play a role in disease progression and persistence. [30][31][32][33] However, the study of ONNV has received relatively little attention since its discovery, though it was the cause of one of the largest known arboviral outbreaks in the late 1950s and early 1960s in Uganda. Other than its clinical symptoms, very little is known about the pathogenesis of ONNV virus compared with CHIKV and RRV.…”

Chikungunya and Its Interaction With the Host Cell

“…According to these findings, Chaaithanya and colleagues (2011) and Kelvin and colleagues (2011) reported high levels of Th1-type cytokines in the blood of patients with chronic disease [86,87]. Thus, despite certain discrepancies, the available studies suggest that chronic disease is associated with a de-regulation of inflammation during the acute and convalescence phases.…”

“…Several studies have tried to identify the factors associated with chronic Chikungunya disease in groups of patients in Singapore [83], La Réunion [84], Dakshina Kannada (India) [85,86], and Emilia Romagna (Italy) [87]. Regulatory mechanisms silencing the vigorous (even localized) inflammatory response seem to be required to prevent the establishment of chronic disease weeks or even months after viral clearance from the blood.…”

Emerging alphaviruses in the Americas: Chikungunya and Mayaro

“…Regulatory mechanisms that impair a vigorous joint infl ammatory response may prevent chronic disease. High levels of Th1-type cytokines in the blood of patients could also be related to chronic arthropathy 18 . Thus, the chronic disease produced by CHIKV is likely induced by deregulated infl ammation during the acute phase of disease and/ or convalescence.…”