COVID-19 Variant Supplement - The role of interleukin-10 responsiveness in lung inflammation in SARS CoV2 infection

A subset of patients infected by SARS CoV2 respond with overproduction of inflammatory cytokines which contribute to their acute respiratory distress and morbidity. This "cytokine storm" results from the imbalance between inflammatory and anti-inflammatory mechanisms. One of these mechanisms involve inflammatory macrophages which produce cytokines such as interleukin-6 and interleukin-1, and anti-inflammatory, regulatory macrophages which predominantly produce the anti-inflammatory cytokine interleukin-10 (IL10). IL10 acts on the inflammatory macrophages to temper their response. We propose to examine whether the regulatory, IL10-producing macrophages in the lung are producing appropriate levels of IL10, or whether the inflammatory macrophages are impaired in their ability to respond to IL10. We will also assess whether a small molecule SHIP1 agonist which activates the intracellular protein SHIP1 like IL10 does, can mimic the action of IL10 and reduce inflammation in SARS CoV2 infection.