IL-18: a suggested target for immunomodulation in chikungunya virus infection
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BRIEF REPORT
IL‑18: a suggested target for immunomodulation in chikungunya virus infection Chintana Chirathaworn1,2 · Jira Chansaenroj2 · Pornsuri Pongsuchart2 · Yong Poovorawan2 Received: 25 March 2020 / Accepted: 8 September 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract Chronic joint pain is the most common pathology found in chikungunya virus (CHIKV)-infected patients. Eight cytokines were compared in CHIKV patients with and without joint pain. IL-4 and IL-13 levels were significantly lower in patients with joint pain (p = 0.006 and p < 0.0001, respectively). IL-18 levels were higher in the group of patients with joint pain (p < 0.0001) and were significantly higher on days 3 and 4 after onset (p = 0.0012 and p = 0.003, respectively). Moreover, TNF-α levels were significantly higher in patients with joint pain on day 3 (p = 0.028). This study demonstrated that cytokines, particularly IL-18, may be candidates for immunomodulation. Chikungunya virus (CHIKV) is an RNA virus belonging to the genus Alphavirus, family Togaviridae. It can be transmitted to humans by Aedes aegypti and Aedes albopictus mosquitoes. CHIKV is an enveloped virus with a positive-sense RNA genome. The 11.8-kb genome encodes non-structural proteins (nsP), a capsid (C) protein and envelope (E) proteins [1, 2]. After it was first reported in Tanzania in 1952, the infection caused by CHIKV emerged in several countries [3, 4]. Patients with CHIKV infection present with fever, headache, fatigue, and arthralgia. Chronic arthralgia is the most common symptom found in CHIKV-infected patients. Currently, there is no specific antiviral or vaccine against CHIKV. Because patients with CHIKV infection present with symptoms similar to rheumatoid arthritis, immune responses in CHIKV infection have been a focus of research [5–7]. Several cytokines have been shown to be associated with CHIKV symptoms [8–10]. Clearly understanding the immune responses in relation to CHIKV infection severity could provide information on targets for therapy that could
Handling Editor: Patricia Aguilar. * Yong Poovorawan [email protected] 1
Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
2
reduce suffering from joint pain induced by this infectious agent. Outbreaks of CHIKV infection occurred in the southern part of Thailand in June 2018 and in Bangkok in October 2018 [11]. A large-scale outbreak developed in the whole country in 2019 [12]. Most patients in this outbreak presented with joint pain. However, there were some patients who only had fever and rash as clinical symptoms, and they did not complain of joint symptoms. In this study, we compared cytokine levels in patients with and without joint pain to elucidate the role of immune responses in CHIKV infection severity. Samples from patients infected with CHIKV during the outbreaks in Thailand in
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