Cytokine expression in rhinovirus- vs. respiratory syncytial virus-induced first wheezing episode and its relation to clinical course

Abstract

Rhinovirus (RV) and respiratory syncytial virus (RSV) are common causes of bronchiolitis. Unlike an RSV etiology, an RV etiology is associated with a markedly increased risk of asthma. We investigated the cytokine profiles of RV- and RSV-induced first wheezing episode and their correlation with prognosis. We recruited 52 sole RV- and 11 sole RSV-affected children with a severe first wheezing episode. Peripheral blood mononuclear cells (PBMCs) were isolated during acute illness and 2 weeks later and stimulated in vitro with anti-CD3/anti-CD28. Culture medium samples were analyzed for 56 different cytokines by multiplex ELISA. Recurrences were prospectively followed for 4 years. In adjusted analyses, the cytokine response from PBMCs in the RV group was characterized by decreased expression of interleukin 1 receptor antagonist (IL-1RA), interleukin 1 beta (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) and increased expression of eosinophil chemotactic protein 2 (eotaxin-2), thymus- and activation-regulated chemokine (TARC), and epithelial-derived neutrophil-activating peptide 78 (ENA-78) in the acute phase and increased expression of fractalkine in the convalescent phase compared to those in the RSV group. An analysis of the change in cytokine expression between study points revealed an increased expression of fractalkine and IL-1β and decreased expression of I-309 (CCL1) and TARC in the RV group compared to those in the RSV group.. Considering hospitalization time, a significant non-adjusted group × cytokine interaction was observed in the levels of interferon gamma (IFN-γ), macrophage-derived chemokine (MDC), IL-1RA, and vascular endothelial growth factor (VEGF), indicating that a higher expression of cytokine was associated with shorter hospitalization time in the RSV group but not in the RV group. A significant interaction was also found in interleukin 6 (IL-6), but the cytokine response was not associated with hospitalization time in the RSV or RV group. In the RV group, increased expression of I-309 (CCL1) and TARC was associated with fewer relapses within 2 months, and decreased expression of interleukin 13 (IL-13) and increased expression of I-309 (CCL1) were associated with less relapses within 12 months. Differences in cytokine response from PBMCs were observed between RV- and RSV-induced first severe wheezing episode. Our findings also reveal new biomarkers for short- and medium-term prognosis in first-time wheezing children infected with RV or RSV.

Identification of systemic biomarkers and potential drug targets for age-related macular degeneration

“…It binds to the C-C motif receptor 8 (CCR8). In addition, it has been implicated in various inflammation-associated diseases, including asthma ( Hurme et al, 2022 ), rheumatoid arthritis ( White et al, 2013 ), and multiple sclerosis ( Schropp et al, 2023 ). In asthma, CCL1 is thought to play a role in recruiting inflammatory cells to the airways, leading to airway inflammation and hyperresponsiveness.…”

Human bocavirus 1 coinfection is associated with decreased cytokine expression in the rhinovirus‐induced first wheezing episode in children

“…Further, peripheral whole blood was collected and PBMCs were isolated during the acute illness and convalescence phase by Ficoll‐Paque™ PLUS (GE Healthcare, Amersham, United Kingdom) density gradient centrifugation according to the manufacturer's instructions. Peripheral blood mononuclear cells were processed and stored as described earlier 26 . In short, samples were stimulated for 24 h with 0.25 μL of anti‐CD3 (1 μg/mL) and anti‐CD28 (1 μg/mL) (BD Biosciences, Franklin Lakes, NJ, USA).…”

“…To ensure that the conclusions were drawn from a majority of the samples, we decided to only include cytokines that were detected (within the limit of quantification) in more than 50% of the samples for analyses (29/56, 52%). If a sample had a value below the limit of detection, they would be set to half the value of the lower threshold of the assay 26–28 . On the other hand, samples exceeding the limit of detection were assigned to the upper threshold of the assay 26,29 .…”

“…Peripheral blood mononuclear cells were processed and stored as described earlier. 26 In short, samples were stimulated for 24 h with 0.25 μL of anti‐CD3 (1 μg/mL) and anti‐CD28 (1 μg/mL) (BD Biosciences, Franklin Lakes, NJ, USA). The supernatants were stored at −80°C.…”

“…If a sample had a value below the limit of detection, they would be set to half the value of the lower threshold of the assay. 26 , 27 , 28 On the other hand, samples exceeding the limit of detection were assigned to the upper threshold of the assay. 26 , 29 The minimum and maximum quantifiable values of the multiplex assays are presented in Supplementary Tables S2 and S3 .…”