A new Review published in Ferroptosis and Oxidative Stress ( FOS ) explores the complex relationship between oxidative stress and inflammation, highlighting how reactive oxygen species can influence inflammatory signaling in highly context-dependent ways.
Reactive oxygen species (ROS) are widely associated with inflammation, but their relationship is far more complex than a simple cause-and-effect process. ROS can act as signaling molecules under physiological conditions, while excessive or mislocalized ROS can damage cellular components and contribute to inflammatory responses.
In the Review “ Oxidative stress and inflammation: A panoply of pathways but a paucity of perspective ” Aoife Costigan and Seamus J. Martin from Trinity College Dublin, Ireland , examine how ROS can influence multiple inflammatory pathways and why the biological consequences of oxidative stress can vary substantially between different cellular and disease contexts.
How does oxidative stress influence inflammation?
The authors highlight several major signaling systems through which ROS can shape inflammatory responses, including NF-κB, Nrf2, HIF-1, cGAS-STING, and the NLRP3 inflammasome.
Rather than acting through a single pathway, ROS can modify redox-sensitive proteins, influence transcription factors, alter cellular signaling, and contribute to DNA and membrane damage. These effects can ultimately reshape inflammatory responses and determine whether cells adapt to oxidative stress or progress toward tissue damage and cell death.
One important example is Nrf2 , a central regulator of cellular antioxidant defenses. While Nrf2 activation is generally considered protective against oxidative stress, the Review highlights evidence that its effects on inflammation can vary depending on the cellular context, intensity and duration of activation, and other biological factors.
The authors also discuss how ROS-associated DNA damage can engage cGAS-STING signaling, while oxidative stress and hypoxia can converge on HIF-1, linking redox regulation with inflammatory responses.
More than just “too much ROS”
A key message of the Review is that the biological effects of oxidative stress cannot be understood simply by measuring the overall amount of ROS.
Where ROS is generated, which type of ROS is involved, which cells are exposed, and how far the redox state has shifted from normal homeostasis may all influence the resulting inflammatory response.
This context dependence may help explain why attempts to broadly suppress oxidative stress have produced inconsistent outcomes in some disease settings.
By bringing together diverse redox-sensitive pathways, the authors provide a broader framework for understanding the molecular links between oxidative stress and inflammation.
Implications for redox and disease research
Oxidative stress and inflammation are closely associated with numerous pathological conditions, including cancer and chronic inflammatory diseases. A better understanding of how ROS is translated into inflammatory signaling could therefore help identify more precise therapeutic strategies.
Rather than viewing ROS simply as harmful byproducts of inflammation, this Review emphasizes their role as dynamic regulators of cellular signaling whose effects depend strongly on biological context.
The work highlights an important question for future research: not simply whether ROS causes inflammation, but how, where, and under what conditions ROS shapes inflammatory responses.
Ferroptosis and Oxidative Stress
Literature review
Cells
Oxidative stress and inflammation: A panoply of pathways but a paucity of perspective
3-Aug-2026
Seamus J. Martin is an Editorial Board Member of Ferroptosis and Oxidative Stress. The other author declares no conflicts of interest.