Sirolimus alters lung pathology and viral load following influenza A virus infection

被引:29
作者
Alsuwaidi, Ahmed R. [1 ]
George, Junu A. [1 ]
Almarzooqi, Saeeda [2 ]
Hartwig, Stacey M. [3 ,4 ]
Varga, Steven M. [3 ,4 ]
Souid, Abdul-Kader [1 ]
机构
[1] United Arab Emirates Univ, Dept Pediat, Coll Med & Hlth Sci, Al Ain, U Arab Emirates
[2] United Arab Emirates Univ, Dept Pathol, Coll Med & Hlth Sci, Al Ain, U Arab Emirates
[3] Univ Iowa, Dept Pathol, Dept Microbiol & Immunol, Iowa City, IA 52242 USA
[4] Univ Iowa, Interdisciplinary Grad Program Immunol, Iowa City, IA USA
来源
RESPIRATORY RESEARCH | 2017年 / 18卷
关键词
Rapamycin; Influenza A virus; Viral replication; Inflammatory score; Lung function; RAPAMYCIN; PNEUMONIA; MODEL;
D O I
10.1186/s12931-017-0618-6
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Background: Inhibitors of mTOR, such as sirolimus, have been shown to induce thymus involution and inflammatory lung disease in mice. The latter effect supports the role of this serine/threonine kinase in ameliorating lung inflammation. Other studies have shown sirolimus reduces/delays lung disease associated with various strains of influenza A virus (IAV). Thus, the effects of mTOR inhibitors on influenza infection deserve further studies. Methods: Here, we examined the changes in lung viral copies, pathology and pulmonary function associated with IAV (A/PR/8/34) infection in mice treated with sirolimus. Results: Body weight loss peaked between days 6-11 post-infection and was more severe in IAV-infected mice that were administered sirolimus as compared to mice that received IAV alone (p = 0.030). Natural log viral gene copies, mean +/- SD per mg lung tissue, in IAV-infected mice that were administered sirolimus were 17.31 +/- 1.27 on day 4, 19.31 +/- 7.46 on day 10, and 0 on day 25. The corresponding number of copies in mice that received IAV alone were 18.56 +/- 0.95 on day 4 (p = 0.132), 1.52 +/- 1.39 on day 10 (p = 0.008), and 0 on day 25. Lung pathology was evident on days 4, 10, and 25 post infection, with mean +/- SD inflammatory score of 9.0 +/- 4.5 in IAV-infected mice that were administered sirolimus, as compared to 11.5 +/- 4.5 (p = 0.335) in mice received IAV alone (maximum score, 26.0). Impaired lung function was evident in IAV-infected mice on days 4 and 10, as demonstrated by increased airway resistance and decreased compliance. Conclusions: In this model, the effects of sirolimus on influenza infection included severe weight loss and modified viral replication, respiratory function and lung inflammation. The adverse events associated with sirolimus treatment are consistent with its potent immunosuppressive activity and, thus, preclude its use in IAV infection.
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