NLRP3 inhibitor dopamine receptors agonist as a potential therapeutic strategy for treatment of overactive immune responses in COVID-19

Abstract

Patients infected with coronavirus disease 2019 (COVID-19) have high serum levels of proinflammatory cytokines. The “cytokine storm” has become one of the major causes of death for critically ill patients infected by COVID-19. Glucocorticoids, plasma from convalescent patients, blood purification, and tocilizumab are currently recommended for use when the body’s inflammatory response is overactivated. However, there are limitations in terms of medicinal effects, equipment reserves, and treatment expense. These challenges prompted us to assess classical agents with good safety and mature production technology. A recent study showed that nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat (LRR)-, and pyrin domain-containing protein 3 (NLRP3) inflammasomes drive COVID-19 pathology. We speculate that suppression of NLRP3 inflammasome-derived cytokine production may be beneficial in COVID-19–infected patients. Dopamine receptors are present in almost all immune cells and can modulate their activation, proliferation, and cytokine production of immune cells. Previous studies have shown that dopamine receptor agonists can control systemic inflammation through inhibition of the NLRP3 inflammasome. This suggests that dopamine receptor agonists may be a new strategy for the treatment of overactive immune responses in COVID-19 patients. This is worthy of further investigation in clinical practice.