Cytokines in the Respiratory Airway as Biomarkers of Severity and Prognosis for Respiratory Syncytial Virus Infection: An Update

Abstract

The human respiratory syncytial virus (hRSV) is one of the most important causes of upper and lower respiratory tract infections in children and the main cause of bronchiolitis worldwide. Disease manifestations caused by hRSV may vary from mild to severe, occasionally requiring admission and hospitalization in intensive care units. Despite the high morbidity rates associated to bronchiolitis, treatment options against hRSV are limited and there are no current vaccination strategies to prevent infection. Importantly, the early identification of high-risk patients can help improve disease management and prevent complications associated with hRSV infection. Recently, the characterization of pro- and anti-inflammatory cytokine patterns produced during hRSV-related inflammatory processes has allowed the identification of potential prognosis biomarkers. A suitable biomarker should allow predicting the severity of the infection in a simple and opportune manner and should ideally be obtained from non-invasive samples. Among the cytokines associated with hRSV disease severity, IL-8, interferon-alpha (IFN-alpha), and IL-6, as well as the Th2-type cytokines thymic stromal lymphopoietin (TSLP), IL-3, and IL-33 have been highlighted as molecules with prognostic value in hRSV infections. In this review, we discuss current studies that describe molecules produced by patients during hRSV infection and their potential as biomarkers to anticipate the severity of the disease caused by this virus.

Rhein Suppresses Lung Inflammatory Injury Induced by Human Respiratory Syncytial Virus Through Inhibiting NLRP3 Inflammasome Activation via NF-κB Pathway in Mice

“…It remains unknown of the precise pathogenetic mechanisms of RSV that causes disease. The main clinical expression of RSV infection is excessive inflammatory and tissue damage (Lee et al, 2017;Vázquez et al, 2019). The release of pro-inflammatory cytokines usually causes excessive inflammatory response, mainly including interleukin IL-1b, IL-6, tumor necrosis factor (TNF-a) (Sun et al, 2018), and other members of the IL-1 gene family, for example, IL-18, IL-33 (Han et al, 2017;Yaneisi et al, 2019), etc.…”

“…The main clinical expression of RSV infection is excessive inflammatory and tissue damage (Lee et al, 2017;Vázquez et al, 2019). The release of pro-inflammatory cytokines usually causes excessive inflammatory response, mainly including interleukin IL-1b, IL-6, tumor necrosis factor (TNF-a) (Sun et al, 2018), and other members of the IL-1 gene family, for example, IL-18, IL-33 (Han et al, 2017;Yaneisi et al, 2019), etc. The Pulmonary inflammation and injury maybe caused by inflammasome activation, which can be resulted from viral infection of RSV infection (Yoo et al, 2013;Triantafilou and Triantafilou, 2014;Rivera-Toledo et al, 2017;Segovia et al, 2017).…”

IL-33 and ST2 as predictors of disease severity in children with viral acute lower respiratory infection

“…In a recent review by Vázquez et al [23], the authors highlight the importance of early identification of high-risk patients in the management of RSV disease in infants and young children, as treatment options are scarce. In this paper, IL-33 is mentioned as a potential biomarker of disease severity.…”

The role of M2‐2 PDZ‐binding motifs in pulmonary innate immune responses to human metapneumovirus

“…Both are generally suggested to be associated with the disease severity of HMPV and respiratory syncytial virus (RSV). [32][33][34][35][36][37][38][39][40] Although the attenuation of mutant replication ( Figure 1A) and enhanced induction of protective immune mediators, such as IL12-p40, 33 could prevent severe lung injury from possible adverse effects of mutant-enhanced inflammatory cytokines, there are three recent publications from different groups, who supported that higher innate cytokines triggered by an essential amount of infectious particles are necessary to prevent severe RSV diseases. [41][42][43] Viruses with a low inoculation indeed can cause more severe disease because of their failure to induce sufficient innate immune responses, demonstrating complicated balance mechanisms underlying disease severity.…”