# Swollen Feet: Considering the Paradoxical Roles of Interleukins in Nephrotic Syndrome

## TL;DR

This review explores how certain interleukins, typically linked to inflammation, can also protect kidney cells in nephrotic syndrome.

## Contribution

The paper highlights the novel cytoprotective roles of IL-1R- and IL-Rγc-signaling interleukins in podocyte survival.

## Key findings

- Pro-inflammatory cytokines can exert anti-apoptotic effects in podocytes via the PI-3K/AKT pathway.
- Some interleukins may serve as potential therapeutics for podocytopathy in nephrotic syndrome.
- The dual roles of interleukins in both damaging and protecting podocytes remain complex and require further study.

## Abstract

Interleukins are a family of 40 bioactive peptides that act through cell surface receptors to induce a variety of intracellular responses. While interleukins are most commonly associated with destructive, pro-inflammatory signaling in cells, some also play a role in promoting cellular resilience and survival. This review will highlight recent evidence of the cytoprotective actions of the interleukin 1 receptor (IL-1R)- and common gamma chain receptor (IL-Rγc)-signaling cytokines in nephrotic syndrome (NS). NS results from the injury or loss of glomerular visceral epithelial cells (i.e., podocytes). Although the causes of podocyte dysfunction vary, it is clear that pro-inflammatory cytokines play a significant role in regulating the propagation, duration and severity of disease. Pro-inflammatory cytokines signaling through IL-1R and IL-Rγc have been shown to exert anti-apoptotic effects in podocytes through the phosphoinositol-3-kinase (PI-3K)/AKT pathway, highlighting the potential utility of IL-1R- and IL-Rγc-signaling interleukins for the treatment of podocytopathy in NS. The paradoxical role of interleukins as drivers and mitigators of podocyte injury is complex and ill-defined. Emerging evidence of the cytoprotective role of some interleukins in NS highlights the urgent need for a nuanced understanding of their pro-survival benefits and reveals their potential as podocyte-sparing therapeutics for NS.