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High altitude hypoxia is known to induce an inflammatory response in immune cells. Hypoxia induced inflammatory chemokines may contribute to the development of high altitude pulmonary edema (HAPE) by causing damage to the lung endothelial cells and thereby capillary leakage. In the present study, we were interested to know whether chronic inflammation may contribute to HAPE susceptibility. We examined the serum levels of macrophage inflammatory protein-1α (MIP-1α), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 in group (1) HAPE Susceptible subjects (n = 20) who had past history of HAPE and group (2) Control (n = 18) consist of subjects who had stayed at high altitude for 2 years without any history of HAPE. The data obtained confirmed that circulating MCP-1, MIP-1α were significantly upregulated in HAPE-S individuals as compared to the controls suggestive of chronic inflammation. However, it is not certain whether chronic inflammation is cause or consequence of previous episode of HAPE. The moderate systemic increase of these inflammatory markers may reflect considerable local inflammation. The existence of enhanced level of inflammatory chemokines found in this study support the hypothesis that subjects with past history of HAPE have higher baseline chronic inflammation which may contribute to HAPE susceptibility.

Dengue is an arboviral disease with no effective therapy available. Therefore, there is an urgent need to find a potent antiviral agent against dengue virus (DENV). In the present study, salidroside, a main bioactive compound of Rhodiola rosea, was evaluated for its antiviral potential against DENV serotype-2 infection and its effect on host innate immune factors. Antiviral effects of salidroside were examined in DENV-infected cells by western blotting, flow cytometry and real-time PCR. Its underlying mechanism involved in antiviral action was determined by evaluating expression of host innate immune factors including RIG-I, IRF-3, IRF-7, PKR, P-eIF2α and NF-κB. Salidroside potently inhibited DENV infection by decreasing DENV envelope protein expression more than tenfold. Salidroside exerts its antiviral activity by increasing expression of RNA helicases such as RIG-I, thereby initiating a downstream signaling cascade that induces upregulation of IRF-3 and IRF-7. It prevents viral protein synthesis by increasing the expression of PKR and P-eIF2α while decreasing NF-κB expression. It was also found to induce the expression of IFN-α. In addition, the number of NK cells and CD8 T cells were also found to be increased by salidroside treatment in human PBMCs, which are important in limiting DENV replication during early stages of infection. The findings presented here suggest that salidroside exhibits antiviral activity against DENV by inhibiting viral protein synthesis and boosting host immunity by increasing the expression of host innate immune factors and hence could be considered for the development of an effective therapeutic agent against DENV infection.

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