Acute-Phase Levels of CXCL8 as Risk Factor for Chronic Arthralgia Following Chikungunya Virus Infection

Abstract

The immunopathogenesis of chikungunya virus (CHIKV) infection and the role of acute-phase immune response on joint pain persistence is not fully understood. We investigated the profile of serum chemokine and cytokine in CHIKV-infected patients with acute disease, compared the levels of these biomarkers to those of patients with other acute febrile diseases (OAFD) and healthy controls (HC), and evaluated their role as predictors of chronic arthralgia development. Chemokines and cytokines were measured by flow Cytometric Bead Array. Patients with CHIKV infection were further categorized according to duration of arthralgia (≤ 3 months vs >3 months), presence of anti-CHIKV IgM at acute-phase sample, and number of days of symptoms at sample collection (1 vs 2-3 vs ≥4). Patients with acute CHIKV infection had significantly higher levels of CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-1β, IL-6, IL-12, and IL-10 as compared to HC. CCL2, CCL5, and CXCL10 levels were also significantly higher in patients with CHIKV infection compared to patients with OAFD. Patients whose arthralgia lasted > 3 months had increased CXCL8 levels compared to patients whose arthralgia did not (p<0.05). Multivariable analyses further indicated that high levels of CXCL8 and female sex were associated with arthralgia lasting >3 months. Patients with chikungunya and OAFD had similar cytokine kinetics for IL-1β, IL-12, TNF, IFN-γ, IL-2, and IL-4, although the levels were lower for CHIKV patients. This study suggests that chemokines may have an important role in the immunopathogenesis of chronic chikungunya-related arthralgia.

TLR4 is one of the receptors for Chikungunya virus envelope protein E2 and regulates virus induced pro-inflammatory responses in host macrophages

“…In addition to the mice model, earlier reports are also available on the CHIKV-driven pro-inflammatory cytokine burst and associated symptoms in human patient studies, in vivo ( 20 , 21 ). Accordingly, the effect of TLR4 inhibition could be further explored in experimental in vitro or in vivo setups with CHIKV-infected patient samples.…”

What Do We Need to Know About Musculoskeletal Manifestations of COVID-19?

“…Another potential limitation lies in the fact that it is extremely difficult to establish causal links between COVID-19 and certain musculoskeletal manifestations, since multiple confounding factors are usually present in this complex scenario. Nevertheless, viral myositis and other musculoskeletal disorders have been commonly seen in patients infected with other viruses (e.g., influenza, acute hepatitis B, chikungunya, Zika, and dengue fever) 103-105 .…”

Serum Soluble Mediator Profiles and Networks During Acute Infection With Distinct DENV Serotypes

“…It has been shown that together with IL-6, CXCL8 mediates the derangement of coagulation and fibrinolysis acts and synergistically in the upregulation of tissue factors by endothelial cells ( 30 ). Clinical studies in endemic areas have described a correlation between DENV disease outcome and the levels of CCL4 which are intimately related to hypotension, thrombocytopenia, and hemorrhagic shock ( 14 , 41 ). In general, the studies demonstrated that IL-12 seems to play a protective role during DENV-2 infection, preceding IFN-γ production ( 36 ).…”