Journal of Clinical Investigation: Lipid Mediators of Disease

Overview

• Uncontrolled inflammation is a significant component of various diseases including arthritis, cardiovascular diseases, neurodegenerative diseases, asthma, cancer, metabolic syndromes, and autoimmune diseases.
• Acute inflammatory response is protective, with neutrophils (PMNs) acting as first responders. Excessive PMNs can lead to tissue damage and chronic inflammation.
• Resolution phase of inflammation: involves reducing PMNs and utilizing specialized mediators to restore tissue function.
• Current treatments: Involve NSAIDs, which have side effects prompting the need for alternative treatments.

Specialized Pro-Resolving Mediators (SPMs)

• Families of SPMs: Includes resolvins, protectins, and maresins.
• Roles:
  • Stimulate self-limited responses
  • Enhance microbial clearance
  • Are organ-protective
• Biosynthesis: SPMs are biosynthesized from omega-3 PUFAs like DHA and EPA.

Mechanisms and Actions

• SPMs in Resolution: Act as stop signals in inflammation and enhance clearance of immune cells.
• SPM Receptors: Key receptors include ALX/FPR2, ERV1, DRV1, and DRV2 which mediate anti-inflammatory actions.
• Resolution Indices: Include metrics to evaluate resolution effectiveness like PMN reduction.

SPMs in Disease and Treatment

• SPMs in Infections: Enhance inflammation resolution and reduce antibiotic needs.
• Organ Protection: SPMs protect against organ damage in ischemia/reperfusion injuries and infections.
• Therapeutic Potential: SPMs offer new avenues for treating inflammatory diseases without the side effects of immunosuppression.

Research and Applications

• Human Studies: SPMs have been identified in various human tissues and fluids.
• Therapeutic Development: Stable SPM analogs are being developed for clinical use in conditions like dry eye syndrome and periodontal disease.
• Dietary Implications: Omega-3 supplementation can affect SPM levels and promote resolution of inflammation.

Conclusion

• SPMs offer a promising therapeutic pathway to address inflammation-related diseases, with ongoing research needed to understand their full potential and application in human health.

References

• Various studies and patents are referenced to support the findings and ongoing research into SPMs and their clinical applications.