Anti-Inflammatory Effect of Thalidomide on H1N1 Influenza Virus-Induced Pulmonary Injury in Mice
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Anti-Inflammatory Effect of Thalidomide on H1N1 Influenza Virus-Induced Pulmonary Injury in Mice Haiyan Zhu,1 Xunlong Shi,1 Dianwen Ju,1 Hai Huang,1 Wei Wei,2 and Xiaoying Dong2,3
Abstract—The purpose of this study is to investigate the anti-inflammatory effect of thalidomide (Thd) on H1N1-induced acute lung injury in mice. BALB/C mice were infected intranasally with influenza A virus (H1N1) and then treated with Thd at a dose of 100 or 200 mg/kg/day for 7 days. Weight loss and survival of mice were monitored for 14 days after virus challenge, and the serum and lung tissues were collected at 4 days for histological and biochemical analysis. The results showed that Thd significantly improved the survival rate, reduced the infiltration of inflammatory cells and cytokine (e.g., IL-6, TNFα) and chemokine (e.g., RANTES, IP-10) levels, and inhibited activated p-NFκB p65 in infected mice. These findings suggested that Thd may attenuate H1N1-induced pulmonary injury and thus may find use in the treatment of viral diseases. KEY WORDS: thalidomide; influenza virus; lung injury; H1N1; anti-inflammation.
INTRODUCTION Influenza viruses may cause acute respiratory disease with significant morbidity and mortality each year. In 2009, a novel influenza A (H1N1) virus emerged in Mexico and then spread rapidly worldwide, leading the World Health Organization to declare a phase-6 pandemic alert [1]. It has been well documented that the pathogenicity of influenza virus is associated with the expression of cytokines/ chemokines [2]. They may be particularly important in the pathological development of viral infection, as the production of cytokines by infected cells seems to be a prerequisite for the initiation of an immune response to control viral replication, and a cytokine storm contributes to severe post-infection complications. A better knowledge of the inflammatory response to influenza A virus infection may help to control the occurrence of complications and to reduce the associated tissue damage [3]. For this reason, 1
Department of Biosynthesis, School of Pharmacy, Fudan University, 826 Zhangheng Road, 201203 Shanghai, China 2 Department of Rheumatism and Immunity, General Hospital of Tianjin Medical University, 300052 Tianjin, China 3 To whom correspondence should be addressed at Department of Rheumatism and Immunity, General Hospital of Tianjin Medical University, 300052 Tianjin, China. E-mail: [email protected]
anti-inflammatory agents have been considered to be important constituents of anti-influenza treatment strategies. Thalidomide (α-N-phthalimidoglutarimide), a glutamic acid derivative initially developed as a sedative, was withdrawn from the market due to its teratogenic effects. However, a number of clinical and experimental studies have demonstrated that thalidomide and its analogs are effective in the treatment of a wide variety of diseases [4], including erythema nodosum leprosum, multiple myeloma, rheumatoid arthritis, Crohn's disease, prostate cancer, and lupus erythematosus [5]. It also showed that interleuk
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