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.
