Carbocisteine inhibits rhinovirus infection in human tracheal epithelial cells

¹ Dept of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, 980-8574
² Virus Research Center, Clinical Research Division, Sendai National Hospital, Sendai 983-8520, Japan

^* To whom correspondence should be addressed. E-mail: yasuda{at}geriat.med.tohoku.ac.jp.

	Abstract

To examine the effects of a mucolytic drug, carbocisteine, on rhinovirus (RV) infection in airways, human tracheal epithelial cells were infected with a major group rhinovirus-RV14. RV14 infection increased virus titers and the content of cytokines in supernatants. Carbocisteine reduced supernatant virus titers and the RNA of RV14 in the cells, the susceptibility to RV infection in the cells, and supernatant cytokine concentrations, including interleukin (IL)-6 and IL-8, after RV14 infection. Carbocisteine reduced the mRNA expression of the intercellular adhesion molecule, (ICAM)-1, the receptor for the major group of RVs. Carbocisteine also reduced the supernatant concentrations of a soluble form of ICAM-1, the number and the fluorescence intensity of acidic endosomes in the cells before RV infection, and reduced the nuclear factor-B activation by RV14. Carbocisteine also reduced the supernatant virus titers of a minor group rhinovirus-RV2, although carbocisteine did not reduce the mRNA expression of a low density lipoprotein receptor, the receptor for RV2. These results suggest that carbocisteine inhibits RV2 infection by blocking the RV RNA entry from the endosomes and inhibits RV14 infection by the same mechanism and by reducing ICAM-1. Carbocisteine may modulate airway inflammation by reducing the production of cytokines in rhinovirus infection.