When well-controlled, the innate immune response is the first line of defence of infections. However, excessive responses cause damage to the body. The term “cytokine storm” portraits an immune response out of control. Cytokine storms are associated with various infectious diseases including COVID-19 and sepsis as well as graft-versus-host disease, inflammatory and autoimmune diseases and has also been a consequence of therapeutic interventions. Inflammation associated with a cytokine storm starts locally and then progresses into a systemic response. Even if the term goes way back, there is still a lack of understanding of the molecular mechansims underlying the concept and its contribution to pathogenesis.

Recently, much attention has been given the role of proinflammatory cytokines in pathology during viral infections and the link to disease severity in Acute Respiratory Distress Syndrome (ARDS), one of the major causes of death in COVID-19 patients. ARDS as a consequence of influenza (including avian influenza - H5N1) or corona viruses (Including SARS and MERS CoVs) is characterized by accumulaiton of inflammatory cells, edema formation and marked increase in cytokines. It has been shown that following a viral infection, low levels of antiviral interferons and high levels of proinflammatory cytokines (IL-1b, IL-6, TNFa and chemokines) are produced. This response is accompanied by increased levels of neutrophils and monocytes in blood and tissue. Several proinflammatory cytokines (including IL-6, IL-8, IL-1b), granulocyte-macrophage colony-stimulating factor, reactive oxygen species (ROS) and chemokines contribute to ARDS.

Administration of LPS to mice induce an acute inflammatory response similar to the response occurring during early stages of septic shock with a massive release of cytokines and chemokine. This is a short and cost-effective model for evaluation of anti-inflammatory properites.