Pentoxifylline and Caffeine as potential immunomodulatory agent for COVID-19 treatment
It is well established that following the entrance of respiratory viruses into the epithelial cell of the lung, the viral antigen will be presented on the cell surface to the cytotoxic CD8+ T cells. These cells are capable of killing infected cells by releasing the proinflammatory cytokines, including IFNγ (Rogers and Williams 2018). Although this process is vital for clearing viral infections, complications can occur as it interferes with uninfected cells as well as lung function. In severe cases, cytotoxic CD8+ T cells and high concentration of the cytokines may cause serious injury to the lung (Bauer et al. 2006).
Amplification of the inflammatory signaling cascade can affect vascular permeability through an increasing influx of more phagocytes such as neutrophils and macrophages, leading to vascular endothelium dysfunction (Sharp et al. 2015). Due to this damage, the capacity of ventilation and gas exchange can be reduced drastically. Consequently, the patient may develop acute respiratory failure and require critical care support (Yang et al. 2018).
Moreover, it was also reported that patients with severe COVID-19 cases in ICU showed high levels of IP10, MCP1, GCSF, and TNFα than non-severe COVID-19 patients, suggesting a possible cytokine storm behind the severity of COVID-19 (Huang et al. 2020). Methylxanthines are known to have immune-modulatory effects at low serum concentration and, therefore can be potentially exploited as immunomodulators (Tilley 2011).