Rhinovirus stimulation of anti-inflammatory cytokines in human bronchial epithelial cells

Kim, Young Chan; Lee, Jae Hyung; Kim, Mi Ok; Kim, Tae Hyung; Sohn, Jang Won; Yoon, Ho Joo; Shin, Dong Ho; Park, Sung Soo

Abstract

BACKGROUND: Rhinovirus is an important precipitating factor in acute exacerbation of asthma and COPD. Rhinovirus has short incubation period, causing transient inflammatory process and then has spontaneous resolution. We hypothesized that alterations in anti-inflammatory cytokines are present at sites of rhinoviral infection and these alterations contribute to the transient nature of rhinovirus-induced inflammation and symptomatology. To test this hypothesis, we characterized time-sequenced alterations in anti-inflammatory cytokines elaboration from human bronchial epithelial cells (HBEC).
METHODS
We compared the ability of rhinovirus-infected HBEC to produce anti-inflammatory cytokines with controls. We infected HBEC, BEAS-2B with rhinovirus 14 obtained from American Type Culture Collection. We harvested the supernatants from rhinovirus infected BEAS-2B cells and the controls at 2hr, 4hr, 8hr, 12hr, 24hr, 48hr from inoculation time. We measured the concentration of interleukin(IL)-1 Ra(receptor antagonist), IL-1 sRII(soluble receptor type II), IL-4, transforming growth factor(TGF)-beta by ELISA kits.
RESULTS
Rhinovirus-infected BEAS-2B cells increased the production of IL-1 Ra, IL-1 sRII from 24hr and produced outstandingly compared with the controls at 48hrs. However, the production of IL-4 and TGF-beta was so minimal that there was no significant difference between the rhinovirus-infected BEAS-2B cells and the controls.
CONCLUSIONS
Our results demonstrate that rhinovirus elaborates the IL-1 Ra and IL-1 sRII but not TGF-beta, IL-4. At the beginning of rhinoviral infection, the elaboration of IL-1 Ra, IL-1 sRII was so minimal but notably increased at 48hrs. with slower kinetics. These results suggest the possibility of rhinovirus- induced IL-1 Ra, IL-1 sRII to contribute to the spontaneous resolution.