Avaliação do perfil de citocinas, quimiocinas e fatores de crescimento nas infecções pelos vírus Zika e Chikungunya

Abstract

Introduction: Zika (ZIKV) and Chikungunya (CHIKV) viruses are reemerging arboviruses that can be transmitted simultaneously to humans. The clinical conditions triggered during infections by these viruses are varied and the deregulation of the immune response may be involved in the pathogenesis and prognosis of these arboviruses. Objective: To evaluate possible immunological biomarkers associated with diseases caused by Zika and Chikungunya viruses. Methodology: A series of cases of individuals infected by ZIKV and CHIKV (n=66) with a control group (n=13) were analyzed, followed up by the rheumatology or infectology services of the University Hospital of Sergipe, in the year 2016 Clinical-epidemiological information and blood samples were collected for molecular diagnosis by real-time RT-PCR (plasma) and for the analysis of 45 immunological mediators by LUMINEX (serum). Comparisons of immunological mediators were performed between groups of monoinfections (ZIKV, CHIKV), coinfections (ZIKV/CHIKV), acute phase infection (acute CHIKV), chronic phase (chronic CHIKV) and healthy controls. Numerical variables were described as mean and standard deviation or median, first quartile and third quartile, meeting the assumption of normality. For categorical variables, simple frequencies and percentage frequencies were used. For differences between two groups, the Mann-Whitney test was used. For correlation analysis, Spearman's correlation was used. For the predictive analysis, a linear regression model was used. All p values < 0.05 were considered statistically significant. Results: There was a predominance of females in all groups analyzed, with no age difference between the participants of the infected groups in relation to the control group. However, individuals in the chronic CHIKV group were older than those in the acute CKIKV group. Increased concentrations of IP-10 and RANTES were demonstrated in all infected individuals regardless of the virus (ZIKV or CHIKV). It was also observed that individuals infected only with ZIKV had lower concentrations of IFN-α, IL-1RA, IL-10 and IP-10 and individuals infected only with CHIKV exhibited higher concentrations of IFN-α, IL-1RA and MCP- 1 than coinfected individuals. Furthermore, some cytokines were only observed in the group of individuals in the chronic phase of CHIKV infection (IL-1α, IL-9, IL-12p70, IL-17A, IL-21, IL-22, IL-27, IL-31, IL-4, GM-CSF and PDGF-BB) and these individuals also had a deficient antiviral response compared to individuals in the acute phase. According to predictive analysis, younger individuals infected with CHIKV in the chronic phase of the disease may have a higher production of growth factors associated with tissue remodeling (VEGF-A, VEGF-D, PDGF-BB, PIGF-1, LIF, SDF-α), as well as individuals over 40 years of age may exhibit an exacerbated inflammatory response via Th1, Th2, Th9, Th17, Th22 cell profiles than individuals in the same age groups infected with CHIKV in the acute phase of the disease. Conclusion: This study describes for the first time the immunological profile in ZIKV/CHIKV co-infection and our findings identified an increase in cytokine concentrations exclusive to the chronic phase of CHIKV infection, as well as estimated rates of increase in cytokine production related to age and age. sex of individuals affected by infections, which may contribute to future studies on the development of new therapeutic targets.