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).