Oxidative Stress

Refers to increased levels of reactive oxygen species (ROS), mostly produced by cellular mitochondria. In non-immune cells, this was previously considered to be a defect and a by-product of oxidative metabolism, but it has now been proven to be part of the cellular stress-response where ROS acts as signal- and effector-molecules. ROS has been shown to mediate the cellular response to hypoxia, starvation, inflammation and infection and also regulates cellular autophagy and the process of autophagic cell-death. In general, increased levels of ROS corresponds to increased levels of cellular stress, and occurs at the expense of ATP-synthesis.

ROS-generation also creates a toxic intracellular environment and a general functional decline, but this is generally considered to be a necessary compromise to preserve cellular homeostasis in stressful conditions. In infection, up-regulated levels of ROS serves anti-microbial functions, especially in leukocytes where it is a prerequisite for efficient elimination of phagocytosed pathogens

Supporting Evidence

• ROS-generation as an anti-microbial function, that might also get exploited by pathogens.¹⁾https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924804/
• Signalling functions of ROS.²⁾https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484374/
• Increased production of ROS in mitochondria occurs at a compromise with ATP-synthesis.³⁾https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605959/

Association with Disease

• Increased levels of ROS in muscle of patients with MPS.⁴⁾https://www.ncbi.nlm.nih.gov/pubmed/23834645
• Exposure of muscle-cells to ROS decreases force-generation capacity.⁵⁾https://www.physiology.org/doi/abs/10.1152/ajpcell.00272.2019
• Evidence of redox-stress in joint-tissues from patients with OA and RA.⁶⁾https://www.sciencedirect.com/science/article/pii/S0925443916000041?via%3Dihub⁷⁾https://www.ncbi.nlm.nih.gov/pubmed/30236789⁸⁾https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051818/⁹⁾https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1064874/
• Increased ROS-production by cells of the intervertebral disc in DDD.¹⁰⁾https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368368/
• Blocking ROS-production forestalls DDD after experimental injury.¹¹⁾https://www.thespinejournalonline.com/article/S1529-9430(21)00079-6/fulltext?dgcid=raven_jbs_aip_email
• A reduced capacity for ROS-synthesis by immune-cells might be involved in RA.¹²⁾https://www.ncbi.nlm.nih.gov/pubmed/19052348
• Enhancement of leukocyte capacity for ROS-generation decreased arthritis in mouse-model.¹³⁾https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1564167/
• Oxidative stress is a prominent feature in AS.¹⁴⁾https://www.ahajournals.org/doi/full/10.1161/01.cir.0000026393.47805.21¹⁵⁾https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572357/