Crosstalk between the renin-angiotensin, complement and kallikrein-kinin systems in inflammation

The renin-angiotensin, complement and kallikrein-kinin systems comprise a multitude of mediators that modulate physiological responses during inflammatory and infectious diseases. This Review investigates the complex interactions between these systems and how these are dysregulated in various conditions, including cardiovascular diseases and COVID-19, as well as their therapeutic implications. During severe inflammatory and infectious diseases, various mediators modulate the equilibrium of vascular tone, inflammation, coagulation and thrombosis. This Review describes the interactive roles of the renin-angiotensin system, the complement system, and the closely linked kallikrein-kinin and contact systems in cell biological functions such as vascular tone and leakage, inflammation, chemotaxis, thrombosis and cell proliferation. Specific attention is given to the role of these systems in systemic inflammation in the vasculature and tissues during hereditary angioedema, cardiovascular and renal glomerular disease, vasculitides and COVID-19. Moreover, we discuss the therapeutic implications of these complex interactions, given that modulation of one system may affect the other systems, with beneficial or deleterious consequences.

Automated summary

This review explores the complex interactions between the renin-angiotensin system, complement system, and kallikrein-kinin system, as well as their dysregulation in different conditions and therapeutic implications. Various mediators modulate the balance between vascular tone, inflammation, coagulation, and thrombosis during severe inflammatory and infectious diseases. These systems play important roles in cell biological functions, such as regulating vascular tone, inflammation, and thrombosis.