The cytokine storm of severe influenza and development of immunomodulatory therapy.

Plain Language Summary

The influenza virus is responsible for millions of severe cases and 250 000–500 000 deaths each year. Newly emerging influenza viruses have continued to challenge medical and public health systems. These infections in humans are accompanied by an aggressive pro-inflammatory response and insufficient control of an anti-inflammatory response, a combination of events called ‘cytokine storm’. The authors review the mechanisms involved with a cytokine storm and note that there is great interest in the association between polymorphisms (individual genetic variations) and host susceptibility, which may help explain why some individuals, but not others, seem relatively resistant to cytokine storm. The authors also review the use of immune modulating treatments and conclude that the most promising therapeutic approach may be a combination of S1PR (sphingosine-1-phosphate receptor 1) agonists¬, PPAR (peroxisome proliferator-activated receptor) agonists, COX-2 (cyclooxygenase-2) inhibitors, and antioxidants, including vitamin C, N-acetylcysteine (NAC), Glycyrrhizin (a compound from liquorice), polyphenols and flavonoids (plant-based antioxidants), and should be further studied in randomised clinical trials.