Administration of the endotoxin Lipopolysaccharide (LPS) or other TLR stimulating agents to mice induce acute inflammatory responses similar to the inflammatory response that occures during the early stages of septic shock and also seen in acute systemic responses in ARDS in COVID-19 patients. Shortly after administration of endotoxin, cytokines and chemokines including TNF-a and IL-6 are released. This model is a fast and cost-effective model for screening of anti-inflammatory properties of test items aimed for treatment of inflammatory and autoimmune conditions.
A massive cytokine release can be experimentally induced in serval ways. Toxic agents activating Pattern Recognition Receptors (PPRs) such as Toll Like Receptors (TLRs) are often used to model the effect of invading pathogens. LPS is one such toxin that is routinly used to activate a systemic inflammatory resonse. These models have fast kinetics and model the acute phase of the cytokine storm. LPS activates TLR4 and mimics aspects of a bacterial infection. This model is often used as an experimental model for sepsis.
Resiquimod (R-848) is an agonist to TLR7 and TLR8 and mimics the cytokine response induced by single stranded RNA and viral infections. Cytokine storm can also be induced by superantigens including anti-CD3 and anti-CD28 antibodies. Binding of superagonist antibodies stimulates T cells without antigen-receptor stimulation.