The cytokine storm of severe influenza and development of immunomodulatory therapy

Cell Mol Immunol. 2016 Jan;13(1):3-10. doi: 10.1038/cmi.2015.74. Epub 2015 Jul 20.

Abstract

Severe influenza remains unusual in its virulence for humans. Complications or ultimately death arising from these infections are often associated with hyperinduction of proinflammatory cytokine production, which is also known as 'cytokine storm'. For this disease, it has been proposed that immunomodulatory therapy may improve the outcome, with or without the combination of antiviral agents. Here, we review the current literature on how various effectors of the immune system initiate the cytokine storm and exacerbate pathological damage in hosts. We also review some of the current immunomodulatory strategies for the treatment of cytokine storms in severe influenza, including corticosteroids, peroxisome proliferator-activated receptor agonists, sphingosine-1-phosphate receptor 1 agonists, cyclooxygenase-2 inhibitors, antioxidants, anti-tumour-necrosis factor therapy, intravenous immunoglobulin therapy, statins, arbidol, herbs, and other potential therapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Antioxidants / therapeutic use
  • Antiviral Agents / therapeutic use*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / immunology
  • Cyclooxygenase Inhibitors / therapeutic use
  • Cytokines / antagonists & inhibitors*
  • Cytokines / genetics
  • Cytokines / immunology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Immunoglobulins, Intravenous / therapeutic use
  • Immunologic Factors / therapeutic use*
  • Immunomodulation*
  • Indoles / therapeutic use
  • Influenza, Human / drug therapy*
  • Influenza, Human / genetics
  • Influenza, Human / immunology
  • Influenza, Human / virology
  • Orthomyxoviridae / drug effects*
  • Orthomyxoviridae / immunology
  • Peroxisome Proliferator-Activated Receptors / antagonists & inhibitors
  • Peroxisome Proliferator-Activated Receptors / genetics
  • Peroxisome Proliferator-Activated Receptors / immunology
  • Plant Preparations / therapeutic use
  • Receptors, Lysosphingolipid / therapeutic use

Substances

  • Adrenal Cortex Hormones
  • Antioxidants
  • Antiviral Agents
  • Cyclooxygenase Inhibitors
  • Cytokines
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Immunoglobulins, Intravenous
  • Immunologic Factors
  • Indoles
  • Peroxisome Proliferator-Activated Receptors
  • Plant Preparations
  • Receptors, Lysosphingolipid
  • umifenovir
  • Cyclooxygenase 2
  • PTGS2 protein, human