Role of nasal nitric oxide in the resolution of experimental rhinovirus infection

被引:80
作者
Sanders, SP
Proud, D
Permutt, S
Siekierski, ES
Yachechko, R
Liu, MC
机构
[1] Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Med, Div Crit Care Med, Baltimore, MD 21205 USA
[3] Univ Calgary, Resp Res Grp, Calgary, AB, Canada
关键词
rhinovirus; common cold; asthma; epithelial cells; inducible nitric oxide synthase; nitric oxide; host defense;
D O I
10.1016/j.jaci.2004.01.755
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: Human rhinovirus (HRV) infections are associated with exacerbations of asthma, chronic obstructive pulmonary disease, and sinusitis. Nitric oxide (NO) might play an important role in host defense through its potent antiviral properties. Previous studies have shown that HRV infection in human subjects increased nasal epithelial expression of type 2 nitric oxide synthase (NOS2), an isoform of the enzyme that produces NO. Objective: We sought to investigate whether increases in exhaled NO (eNO) would accompany the increased NOS2 expression and would be associated with clearance of the virus. Methods: Six human subjects were infected with HRV-16 intranasally. eNO from nasal and lower airways was measured by means of direct measurement at multiple controlled How rates. eNO was monitored at baseline (day 1) and on days 2 to 5, 8, 14, and 42 after infection. Nasal lavages were performed on days 1 to 5 and 8, and nasal scrapings were performed on days 1 to 4. NOS2 mRNA expression in nasal cells was measured by using quantitative real-time RT-PCR. Viral shedding in nasal la age fluid was monitored by using real-time RT-PCR and bioassay. Results: Peak HRV titers and symptom scores were correlated on day 3, and HRV persisted until day 5 (n = 4) or day 8 (n = 2). Infection was associated with transient but significant increases in lymphocytes and monocytes in nasal lavage fluid. Significant increases in both nasal and lower airway eNO concentrations accompanied HRV infection and were positively correlated. Increased nasal eNO concentrations on day 3 were associated with increased expression of NOS2 mRNA in nasal scrapings. Symptom scores on day 4 were inversely correlated with the increases in nasal eNO concentration. Conclusions: We conclude that increased production of NO occurs as part of the host response to HRV infection and speculate that NO plays a beneficial role in viral clearance.
引用
收藏
页码:697 / 702
页数:6
相关论文
共 35 条
[31]  
Slutsky AS, 1999, AM J RESP CRIT CARE, V160, P2104
[32]   Rhinitis and asthma: Evidence for respiratory system integration [J].
Togias, A .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2003, 111 (06) :1171-1183
[33]   The treatment of rhinovirus infections: progress and potential [J].
Turner, RB .
ANTIVIRAL RESEARCH, 2001, 49 (01) :1-14
[34]   SIGNS AND SYMPTOMS IN COMMON COLDS [J].
TYRRELL, DAJ ;
COHEN, S ;
SCHLARB, JE .
EPIDEMIOLOGY AND INFECTION, 1993, 111 (01) :143-156
[35]   Regulation of nitric oxide synthesis by dietary factors [J].
Wu, GY ;
Meininger, CJ .
ANNUAL REVIEW OF NUTRITION, 2002, 22 :61-86