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

Abstract

Background: Rhinovirus (RV)-induced first wheezing episodes in children are associated with a markedly increased risk of asthma. Previous studies have suggested that human bocavirus 1 (HBoV1) may modify RV-induced immune responses in young children. We investigated cytokine profiles of sole RV- and dual RV-HBoV1-induced first wheezing episodes, and their association with severity and prognosis.

Methods: Fifty-two children infected with only RV and nine children infected with dual RV-HBoV1, aged 3-23 months, with severe first wheezing episodes were recruited. At acute illness and 2 weeks later, peripheral blood mononuclear cells were isolated, and stimulated with anti-CD3/anti-CD28 in vitro. Multiplex ELISA was used to quantitatively identify 56 different cytokines at both study points. Patients were prospectively followed for 4 years.

Results: The mean age of the children was 14.3 months, and 30% were sensitized. During the acute illness, the adjusted analyses revealed a decrease in the expression of IL-1b, MIP-1b, Regulated upon activation, normal T cell expressed and presumably secreted (CCL5), TNF-a, TARC, and ENA-78 in the RV-HBoV1 group compared with the RV group. In the convalescence phase, the RV-HBoV1 group was characterized by decreased expression of Fractalkine, MCP-3, and IL-8 compared to the RV group. Furthermore, the hospitalization time was associated with the virus group and cytokine response (interaction p < 0.05), signifying that increased levels of epidermal growth factor and MIP-1b were related with a shorter duration of hospitalization in the RV-HBoV1 coinfection group but not in the RV group.

Conclusions: Different cytokine response profiles were detected between the RV and the RV-HBoV1 groups. Our results show the idea that RV-induced immune responses may be suppressed by HBoV1.

Keywords: bocavirus; bronchiolitis; cytokine; rhinovirus; virus; wheeze; wheezing.

FIGURE 1

Study flow chart. Patients with cytology data were included. HBoV1, human bocavirus‐1; ICU, intensive care unit; PBMC, peripheral blood mononuclear cell; RV, rhinovirus.

FIGURE 2

Differences in cytokine expression levels at the study entry. Data are presented as medians (the lower (Q1) and upper (Q3) quartiles, and data falling outside the Q1–Q3 range are plotted as outliers). Cytokine concentrations are presented as pg/mL. In the difference in cytokine expression, multiple significant differences were observed between the two virus groups (rhinovirus (RV) vs. RV‐HBoV1, all p < 0.05) (A–F).

FIGURE 3

Differences in cytokine expression levels at convalescence phase. Data are presented as medians (the lower (Q1) and upper (Q3) quartiles, and data falling outside the Q1–Q3 range are plotted as outliers). Cytokine concentrations are presented as pg/mL. In the difference in cytokine expression, multiple significant differences were observed between the two virus groups (rhinovirus (RV) vs. RV‐HBoV1, all p < 0.05) (A–C).