Pentoxifylline:
Prior studies have reported that alveolar macrophages release
inflammatory cytokines such as TNF-α that plays an important role in the
prognosis of inflammatory pulmonary diseases
(Kelley 1990;
Sibille and Reynolds 1990). Consistent
with the literature, it has been shown that pentoxifylline elicited a
significant reduction in the production of TNF-α in cultured cells of
LPS -stimulated alveolar macrophages and peripheral blood monocytes
isolated from patients with an indication for bronchoalveolar lavage
(Poulakis et al. 1999). This finding was
also reported by Tong et al. (Tong et al.
2003). The results of this study indicate that pentoxifylline
suppressed TNF-α production in a dose-dependent manner in alveolar
macrophages in sarcoidosis, which is mainly driven by proinflammatory
and anti-inflammatory mediators. Data from another study demonstrated
that pentoxifylline suppressed cytokine-induced neutrophil
chemoattractant, nuclear factor kappa B (NF-κB), Matrix
metalloproteinase-2 (MMP-2), MMP-9 and myeloperoxidase content in
Sprague Dawley rat model (Deree et al.
2007). As mentioned in the literature review, MMPs are well-known
inflammatory mediators that contribute to the aggravation of ALI and
ARDS by accelerating the secretion of neutrophils into the lung
(Torii et al. 1997;
Corbel et al. 2000). This action is
correlated with the proteolytic activity of MMPs.
The efficacy of pentoxifylline in improving the survival rate during
hyperoxia has been shown in neonatal rats
(Almario et al. 2012). Shreds of evidence
suggested that pentoxifylline enhanced the pulmonary antioxidant
activity in enzymes such as glutathione peroxidase, catalase, and
superoxide dismutase. Another important finding was that pentoxifylline
treatment enhanced vascularization through increasing the vascular
endothelial growth factor (VEGF) protein expression
(Almario et al. 2012). It is well
established that VEGF involved in alveolar structures
(Thébaud and Abman 2007). Subsequently,
it has been shown that pentoxifylline not only suppresses
proinflammatory macrophages but also enhances both wound healing and
anti-inflammatory macrophage in nitrogen mustard -induced lung injury
and inflammation (Sunil et al. 2014).
Clinical trial in patients with acute coronary syndromes has shown the
meaningful reduction in pro-inflammatory and elevation of the
anti-inflammatory response following administration of pentoxifylline
400 mg TDS for 6 months. These results suggest the potential therapeutic
efficacy of pentoxifylline in cardiovascular events
(Fernandes et al. 2008).
Considering the extensive evidence on anti-inflammatory and antioxidant
properties of pentoxifylline (Figure 1) , this molecule may have
beneficial clinical effects in COVID-19 patients suffering from the
severe inflammatory response.