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).