Pentoxifylline:
Preliminary randomized clinical trial on pentoxifylline (400 mg, TDS for 12 weeks) demonstrated the enhancement of pulmonary gas exchange in COPD patients. A possible mechanism for these results could have been by the increase in the cardiac output and mixed venous pO2(Haas et al. 1990). A subsequent trial on severe ARDS has shown that administration of pentoxifylline with a dose of 100 mg IV BD for seven days, followed by 400 mg PO TDS, led to the improvement of the symptoms of the ARDS, suppression of mean TNF levels and increasing the survival rate (Montravers et al. 1993).
Furthermore, the efficacy of pentoxifylline in attenuation of acute lung injury has been shown in animal models such as guinea pigs (Lilly et al. 1989). It is also well established that the administration of pentoxifylline at the time of allergen sensitization airway hyperresponsiveness suppresses the allergic inflammation and airway hyperresponsiveness in vivo (Fleming et al. 2001). The observed bronchodilatory, anti-inflammatory, and immunomodulatory properties provide further support for suggesting the pentoxifylline as a promising medicine in severe acute respiratory syndrome (SARS) (Martín et al. 2003).
In a more recent study, pentoxifylline treatment improved ALI-induced by Infrarenal aortic cross-clamping in the Wistar rat model. The proposed mechanism involved the phosphorylation of STAT3, leading to the stimulation of IL-10 production (Li et al. 2016). The beneficial effect of pentoxifylline on lung has been demonstrated in lung cancer patients. A combination of pentoxifylline and vitamin E decreased radiation-induced lung toxicity frequency in lung cancer patients receiving concurrent chemo-radiotherapy (Misirlioglu et al. 2007). These results are in line with those that found the preventive efficacy of the combination, as mentioned earlier in the alleviation of some radiation-induced side-effects in patients with either breast (Magnusson et al. 2009) or head and neck cancer (Sayed et al. 2020). With the massive evidence of lung involvement in COVID-19 patients, pentoxifylline may offer a safe and well-tolerated option to treat the respiratory symptoms in these patients potentially (Figure 1) .