The recent article by Zhu et al. was highly enlightening and thought-stimulating.1 The authors have clearly shown that Heme oxygenase-1 suppresses replication of hepatitis C virus and increases resistance of hepatocytes to oxidant injury.
The findings of Zhu et al. are highly significant because they further corroborate recent studies that suggest that Heme oxygenase-1 may play a major protective role in other systemic inflammatory conditions besides hepatitis C.
For instance, Heme oxygenase-1 increases the synthesis of decay-accelerating factor and thereby attenuates complement-induced endothelial dysfunction in systemic infections.2 Similarly, Heme oxygenase-1 protects tissue such as pulmonary tissue from red blood cell–induced inflammation in lung infections, while increased expression of Heme oxygenase-1 limits systemic damage in septic shock by decreasing endotoxin-induced overexpression of the Type-2 cationic amino acid transporter (CAT-2) enzyme.3 It also inhibits nitric oxide production in endotoxic shock.4 On the other hand, inhibition of Heme oxygenase-1 function has a potent anticarcinogenic influence. For instance, knockdown of Heme oxygenase-1 function by small interfering RNAs has a negative effect on tumor growth in malignancies such as hepatocellular carcinomas.5
Interestingly, a number of factors influence and alter Heme oxygenase-1 levels in the body. For instance, lipopolysaccharide affects the nuclear factor-E2–related factor (nrf2) pathway and thereby accentuates the expression of Heme oxygenase-1 in monocytes, thereby protecting organs such as the liver from damage in severe systemic infections.6 Similarly, hemin arginate induces Heme oxygenase-1 production thereby enhancing hepatic microcirculation and protecting hepatic tissue following septic shock.7
Besides these anti-inflammatory functions, Heme oxygenase-1 also has a major role to play in other hepatic functions. For instance, accentuated Heme oxygenase-1 production decreases ischemia/reperfusion injury in hepatic cells.8 The above examples clearly illustrate the massive therapeutic potential of the anti-inflammatory properties of Heme oxygenase-1. There is a clear and urgent need for further studies to fully elaborate and harness these anti-inflammatory functions of Heme oxygenase-1 for the management of other systemic infections besides hepatitis C.