EXPERIMENTAL RHINOVIRUS-16 INFECTION - EFFECTS ON CELL DIFFERENTIALS AND SOLUBLE MARKERS IN SPUTUM IN ASTHMATIC SUBJECTS

Asthma exacerbations are often associated with respiratory virus infec tions, particularly with rhinovirus. In the present study we investiga ted the effect of experimental rhinovirus 16 (RV16) infection on airwa y inflammation as assessed by analysis of hypertonic saline-induced sp utum. Twenty-seven nonsmoking atopic, mildly asthmatic subjects partic ipated in a placebo-controlled parallel study. RV16 (n = 19) or its di luent (n = 8) was nasally administered. Sputum inductions were perform ed at entry and on Days 2 and 9 after inoculation, and airway responsi veness to histamine (PC20) was measured on Days 4 and 11. Cell differe ntials and levels of albumin, eosinophil cationic protein (ECP), IL-8, and IL-6 were determined. The cellular origin of IL-8 was investigate d by intracellular staining. RV infection was confirmed by culture and /or by antibody titer rise in each of the RV16-treated subjects. There were no significant changes in the sputum differentials of nonsquamou s cells (MANOVA, p greater than or equal to 0.40). In the RV16 group, there was a significant increase in the levels of ECP, IL-8, and IL-6 at Day 2 after infection (p < 0.05), whereas the albumin levels did no t change (p = 0.82). The levels of IL-8 and IL-6 remained elevated for as long as 9 d after infection (p < 0.05). The increase in the percen tage of IL-8 positive cells at Day 2 after infection could be attribut ed to the increase in IL-8 positive neutrophils (p < 0.02). There was a significant decrease in PC20 at Day 4 (p = 0.02), which was no longe r significant at Day 11 (p = 0.19). The decrease in PC20 correlated si gnificantly with the increase in ECP in the first week (r = -0.60) and with the change in the percentage eosinophils in the second week afte r inoculation (r = -0.58). We conclude that experimental RV16 infectio n in atopic asthmatic subjects increases airway hyperresponsiveness in conjunction with augmented airway inflammation, as reflected by an in crease in ECP, IL-8, and IL-6 in sputum. Our results suggest that the RV16-enhanced airway hyperresponsiveness is associated with eosinophil ic inflammation.