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

Leile Camila Jacob-Nascimento, Caroline Xavier Carvalho, Monaíse Madalena Oliveira Silva, Mariana Kikuti, Rosângela Oliveira Anjos, Jordana Rodrigues Barbosa Fradico, Ana Carolina Campi-Azevedo, Laura Beatriz Tauro, Gúbio Soares Campos, Patricia Sousa dos Santos Moreira, Moyra Machado Portilho, Olindo Assis Martins-Filho, Guilherme Sousa Ribeiro, Mitermayer Galvão Reis

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number744183
JournalFrontiers in immunology
StatePublished - Oct 1 2021

Bibliographical note

Funding Information:
This work was supported by the Brazilian National Council for Scientific and Technological Development under Grants 400830/ 2013-2 and 440891/2016-7 to GR, and scholarships to LT, MR, and GR; the Bahia Foundation for Research Support under Grants PET0026/2013, PP0044/2016, and PET0022/2016 to GR, and scholarship to MS; the Coordination for the Improvement of Higher Education Personnel, Brazilian Ministry of Education under grant 88881.130749/2016-01 to GR; the Department of Science and Technology, Secretariat of Science, Technology and Strategic Inputs, Brazilian Ministry of Health; the Federal University of Bahia; the Oswaldo Cruz Foundation; and the REPLICK (Clinical and Applied Research in Chikungunya). OM-F is a research fellow from FAPEAM (PVN-II, PRÓ-ESTADO Program #005/2019). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Funding Information:
The authors thank the technical staff who participated in data collection and sample processing, Renan Rosa for his assistance with data management, the São Marcos Health Unit staff for providing health assistance to the patients, and the patients for their participation in the study. The authors thank the program for technological development in tools for health-PDTIS-FIOCRUZ for the use of its facilities. LJ-N thanks the Coordination for the Improvement of Higher Education Personnel (CAPES) for scholarship grant.

Publisher Copyright:
© Copyright © 2021 Jacob-Nascimento, Carvalho, Silva, Kikuti, Anjos, Fradico, Campi-Azevedo, Tauro, Campos, Moreira, Portilho, Martins-Filho, Ribeiro and Reis.


  • chemokines
  • chikungunya
  • chronic arthralgia
  • cohort
  • cytokines
  • serum biomarkers

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't


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