Pentoxifylline and Caffeine as a potential anti-inflammatory and antioxidant agent for COVID-19
Viral infections, in general, are associated with the constant generation of oxidized products. Previously it has been shown that viral lung pathogens can trigger the oxidative stress pathways resulting in the generation of ROS as well as local production of oxidized phospholipid (OxPL) (Imai et al. 2008). Analysis of humans died in SARS-CoV infections showed the massive formation of OxPLs in all the severe cases of acute lung injury (ALI) (Imai et al. 2008). In a disease model, it was shown that ALI was caused by the overproduction of IL-6 in alveolar macrophages via Toll-like receptor 4 (TLR4)/NF-kB signaling and it was a result of the activated innate immune response due to the SARS-CoV induced production of OxPLs (Imai et al. 2008). In addition to the challenge of ALI due to SARS-CoV, severe acute respiratory distress syndrome (ARDS) treatment is an ongoing challenge for COVID-19 patients infected with SARS-CoV-2 (Matthay et al. 2020). Patients with severe cases of ALI/ARDS are treated in intensive care units (ICUs) and have severe inflammation. Several factors contribute to the inflammation, including hypoxia, due to inflammatory mediators like cytokines and viral infection (Sarma and Ward 2011). Accordingly, we speculate that similar excessive oxidation is likely to be involved in COVID-19 patients. This speculation was further supported by the severe inflammatory response observed in COVID-19 patients with heightened levels of the proinflammatory cytokines like IL-2, IL-4, IL-7, IL-8, IL-9 and also high amounts of IL-1β, IFNγ, IP-10, and MCP-1, which probably points towards an activated T-helper-1 (Th1) cell responses (Huang et al. 2020).