Table 1 Low-cost, readily available drugs with immunomodulatory activities that could benefit patients with severe influenza
From: The dysfunctional host response to influenza A H7N9: a potential treatment option?
Drug class | Proposed mechanism of protection for influenza | Level of evidence |
|---|---|---|
HMG CoA reductase inhibitors (statins); lipid-lowering agents with numerous anti-inflammatory and vasoprotective effects | Alter prenylation pattern of enzymes and membranes: vaso-protection; lower TLR signaling; reduce oxidative stress; upregulate eNOS; upregulate AMPK and PGC-1 alpha; reduce NADPH oxidase activity | Animal studies; numerous observational studies in pneumonia and one in human influenza; one randomized, controlled trial in human sepsis |
Aspirin, a cyclooxygenase inhibitor, might potentiate statin effects | Unknown, may shunt oxygenated lipid precursors to lipooxygenase pathway; might amplify statin actions | Observational studies in patients with severe pneumonia |
PPAR-gamma agonists (thiazolidinediones, glitazones); anti-diabetic treatments with effects on mitochondrial biogenesis | Agonist for PGC-1 alpha that promotes mitochondrial function and biogenesis, might limit apoptosis | Animal studies with influenza virus challenge models |
PPAR-alpha agonists (fibrates); lipid-lowering agents with effects on mitochondrial biogenesis | Promotes mitochondrial function, biogenesis | Animal studies with influenza virus challenge models |
Angiotension II inhibitors – ARB agents and ACE inhibitors | Blocks angiotensin II ligation to AT-1, limiting superoxide generation by NADPH oxidase | Human observational studies in pneumonia patients, no data on influenza patients thus far |
AMPK agonists (metformin), anti-diabetic agents with immune-metabolic effects | AMPK reduces oxidant stress and induces anti-apoptotic signals | Preclinical studies, no data in influenza patients thus far |
Resveratrol, a polyphenol nutritional supplement | Stimulates sirtuin activity, activates PPAR alpha and PGC-1 alpha, protects against oxidant stress | Improved survival in animal studies with influenza challenge models |