Caffeine:
Following the previously published preclinical studies, caffeine showed anti-inflammatory effects in the lungs of rat pups following its administration at a low neonatal dose (Köroğlu et al. 2014). Further preclinical studies showed that caffeine reduced the production of proinflammatory cytokines in a rat model of endotoxic shock (Tofovic et al. 2001) and also suppressed the TNF-α-induced apoptosis and hepatitis in mice model (Sugiyama et al. 2001). Besides, it was also reported in another preclinical study that acute caffeine treatment at a high dose or chronic caffeine treatment at a low dose reduced lung damage and inflammatory cytokines like TNF-α and IL-1 levels in a lung injury mice model. However, a chronic caffeine treatment at a low dose enhanced inflammation and lung damage (Li et al. 2011). On a similar note, in vitro studies showed the presence of coffee extracts on lipopolysaccharide (LPS)-treated murine macrophage-like cells showed a decrease in mRNA levels of TNF-α and IL-6 (Jung et al. 2017). Such an anti-inflammatory effect of caffeine correlates with reduced expression of IL-6, IL-3, and IL-12 by LPS-treated murine macrophage cells (Samieirad et al. 2017). In another study, 50µM caffeine treatment on LPS-activated cord blood (neonatal) monocytes showed a 20% decrease of TNF-α production (Chavez-Valdez et al. 2009) and at a concentration of 100µM caffeine suppressed the TNF-α production by LPS-stimulated human whole blood by approximately 40% (Horrigan et al. 2004). In addition to preclinical and in vitro data, there is epidemiological evidence showing that caffeine intake as a protective factor for diseases like Alzheimer’s disease (Maia and De Mendonça 2002). The neuroprotective effects could be due to its anti-inflammatory properties. The extensive studies showing anti-inflammatory and anti-oxidative properties of caffeine(Figure 2) suggests that it may play a potential therapeutic role and a possible treatment of inflammation and oxidations in COVID-19 patients.