Lipoxins - A Review

Introduction

Various mediators get released as part of the immune response during injury or infection. One such mediator molecule is lipoxin. It is anti-inflammatory and is secreted by immune cells like macrophages and neutrophils. While this is its primary role, they have numerous other roles, such as homeostasis of tissues and immune regulation. They have shown remarkable therapeutic ability. They were discovered around 50 years ago but are still in the research stage for clinical usage. This article aims to study the different mechanisms of synthesis of lipoxins, their functions, and clinical implications.

How Are Lipoxins Synthesized?

There are two major routes from arachidonic acid that synthesize lipoxins. Lipoxygenases are the enzymes helping in this.

1. The first route happens in platelets, where leukotriene is converted to lipoxins.

2. The second route is the arachidonic acid pathway, wherein the lipoxygenases convert them into a series of reactions leading to the formation of lipoxin A and B.

3. Additionally, there is a third route, Aspirin-dependent, which helps in the acetylation of cyclooxygenase, leading to the formation of epi-lipoxins.

What Is Their Role at the Site of Inflammation?

Lipoxins have multiple roles in combating infections, injury, and inflammation.

1. Migration of Neutrophils: Neutrophils come to the site as the first line of defense whenever an injury or infection occurs. Lipoxins also have a role in this by increasing the calcium levels in the cell; this provokes the cytoskeletal elements to come together and helps in the transendothelial migration of the neutrophils.

2. Clearing of Neutrophils: Once the site is cleared and inflammation is resolved, neutrophils must leave the site to avoid further damage. Generally, apoptosis occurs, and delay in this step leads to disorders like cancer, etc. Lipoxins help clear the neutrophils in this step.

3. Inhibition of Stable Anion Formation: Lipoxins have a role in preventing tissue damage by inhibiting the formation of stable anions, which recruit white blood cells to inflamed tissues.

4. Decrease in Neutrophil Count: They indirectly affect interleukin 8, again reducing the accumulation of neutrophils.

What Are the Clinical Implications of Lipoxins?

Lipoxins are specialized lipid mediators that have numerous clinical applications. The applications range from the effect on inflammatory conditions to chronic neurological disorders. Their protective effects on multiple systems make them a promising therapeutic agent in various pathological diseases. Some of the clinical uses are:

1. Inflammatory Conditions: Numeric acute inflammatory conditions, such as sepsis, acute respiratory distress, etc., pose a serious threat due to tissue damage. Lipoxins have shown anti-inflammatory action by increasing the cell in preparation and promoting inflammation resolution.

Chronic inflammatory conditions such as asthma, inflammatory bowel disease, etc, are characterized by dysfunction in immune regulation. Lipoxins have a huge role in repairing tissue damage and dampening immune activation. They function as braking signals in inflammation.

1. Transplantation: Patients undergoing organ transplantation face multiple challenges, such as rejection or inflammatory response. When lipoxins are used, they help promote immune tolerance and suppress the inflammatory reaction by cytokines. This will improve transplant outcomes and significantly reduce the need for immunosuppressive therapies separately, reduce the side effects of the drugs on the patient, and help them in the long run.

2. Wound Healing: Lipoxins have a healing and repair ability by promoting the formation of new blood vessels and collagen deposition. They have pro-resolving property, which enhances the resolution of inflammation and facilitates a smoother transition from inflammatory to the proliferative phases of healing. This property of lipoxins can be utilized in conditions where there is impaired healing of wounds, such as diabetic ulcers and delayed healing wounds.

3. Cardiovascular Diseases: Inflammation and atherosclerosis are the main disease-causing factors leading to cardiac issues. Lipoxins have been studied to resolve both these factors, such as vascular inflammation, reduce the formation of atherosclerotic plaques, and significantly improve metabolic health. They also can regulate lipid metabolism, oxidative stress, and inflammation, making them an important factor in cardiac therapy.

4. Neuroprotective: In patients with Alzheimer’s disease and Parkinson’s disease, lipoxins have shown protective effects. In these disorders, chronic inflammation and oxidative stress are common. Lipoxins have been shown to potentially mitigate any neuronal injury and help preserve cognitive function in invitro studies with similar degenerative changes done. They also work by reducing oxidative stress and modulating neuroinflammatory responses. They are also effective against neuropathic pain and multiple sclerosis. Therefore, lipoxins are a major therapeutic agent in managing most neurological disorders and significantly improving the patient's quality of life.

5. Cancer Inflammation: Studies have shown that treatment with lipoxin in models significantly reduces pro-inflammatory cytokines. It has also been shown to inhibit growth factor-stimulated cell migration. These treatment modalities help identify new targets for treating cancer-related inflammation.

6. Viral Infections: Lipoxins possess some direct antiviral properties. They interfere in virus entry replication. They enhance the activity of immune cells, such as natural killer cells and macrophages. They also modulate adaptive immunity, facilitate virus clearance, and limit the extent of tissue damage.

7. Periodontal Diseases: Lipoxins can inhibit the pro-inflammatory mediators that cause inflammation of the periodontium. Also, as preclinical studies showed, there was a marked decrease in pathogenic bacteria in the mouth after treatment.

What Are the Future Directions?

Lipoxins are showing promising outcomes in various preclinical models. Further understanding the mechanisms of action and signaling pathways can help pave the way for developing novel targeted therapeutic agents specifically for host immune modulation and resolution of inflammation. The preclinical study results must be converted to proper clinical cases and documented for further advances. Various formulations and routes of administration can be modified to look for the best treatment outcome.

Conclusion

To conclude, lipoxins are a class of lipid mediators with a major anti-inflammatory role. They have a marked effect on the immune system, reducing inflammation and promoting tissue repair. Though many studies are preclinical, lipoxins represent a class of novel therapeutic agents that can be utilized against inflammatory diseases, cancer, neurodegenerative diseases, wound healing issues, and viral infections. External administration of lipoxins can also be utilized to heal inflammatory reactions.