I use aspirine + fish oil becouse of this: "An important third mechanism has recently been discovered that produces lipoxins of different stereochemistry, i.e. the epi-lipoxins, sometimes termed the aspirin-triggered lipoxins (‘ATL’), as the reaction is initiated by aspirin and requires the cyclooxygenase COX-2 in the first step. As discussed in the Introduction
to these pages, COX-2 is induced in endothelial and epithelial cells in response to a variety of stimuli. The effect of aspirin is to acetylate the enzyme, switching its catalytic activity (and its chirality) from prostanoid biosynthesis to production of 15R
-HETE rather than the S
-enantiomer. This is in turn converted to 5S
-hydroxy-ETE, as described above for lipoxins, by the action of the 5-lipoxygenase in leukocytes and thence to epi-lipoxins, i.e. epi-LXA4
)-HETE produced by the action of a cytochrome P450 enzyme in the absence of aspirin can also be converted to 15-epi-lipoxins"
Acute inflammation in response to infection or tissue damage is usually characterized by heat, redness, swelling and pain at a simple observational level, and by oedema, accumulation of leukocytes, and then by accumulation of monocytes and macrophages at a cellular level. Leukotrienes (especially LTB4
) and prostaglandins (PGE2
) derived from arachidonic acid are important in the early stages of the inflammatory process. As tissues return to health, resolvins and protectins, together with lipoxins
and maresins, promote resolution of the inflammation through removal of the leukocytes together with cellular debris, ideally without leaving remnants of the host defences or of the invading microorgansms or other inflammatory initiators.
The resolvins and neuroprotectins are distinctive and highly stereospecific lipids, which are endogenous local mediators with strong anti-inflammatory effects in addition to some immunoregulatory activities at picomolar to nanomolar concentrations. They are part of the molecular mechanisms that contribute to removal of inflammatory cells and restoration of tissue integrity once the need for the inflammatory response is over, i.e. they actively assist in the resolution of inflammation, once thought to be a passive process. It is evident that the presence of aspirin uniquely facilitates the resolution of inflammation. Thus, at local sites of inflammation, aspirin treatment enhances the conversion of the omega-3 fatty acids EPA and DHA to 18R
-oxygenated products, i.e. resolvins of the E and D series, which carry potent anti-inflammatory signals. So far two receptors have been identified that mediate the activities of RvE1
During inflammation, polymorphonuclear neutrophils are produced which have generally beneficial effects in countering disease, but in the longer term or if malfunctioning they may eventually cause trauma and tissue damage through infiltration into tissues. The resolvins, like the lipoxins, appear to have an important role in regulating and indeed inhibiting these harmful effects. In so doing they oppose the effects of some of the pro-inflammatory prostanoids. For example, nanomolar concentrations of resolvin E1 dramatically reduce dermal inflammation, peritonitis, dendritic cell migration and interleukin production. RvE1 blocks excessive platelet aggregation, and it also limits the effects of certain human pathogens by enhancing phagocytosis by polymorphonuclear leukocytes. Similarly, RvD2 has extremely potent regulatory actions on neutrophil trafficking in the picogram range in vivo
by stimulating resolution and enhancing innate host defense mechanisms via a specific receptor.
The (neuro)protectins appear to operate in the same way as the resolvins in brain tissue. Thus, (N)PD1 has anti-inflammatory effects and protects retinal epithelial cells from apoptosis induced by oxidative stress. In addition, it has protective effects in animal models of stroke and of Alzheimer's disease. Amongst its activities in non-neuronal tissues, it promotes apoptosis of T cells and it has beneficial effects towards asthma in nanogram amounts. It is evident that such compounds and their metabolism have considerable potential for therapeutic intervention in acute inflammation or chronic inflammatory disease. They may also mitigate the affects of sepsis.
It is now well established that administration of lipoxins, resolvins and protectins in vivo
in animal models can aid the process of recovery from inflammation without compromising host defences by causing immune suppression. It is evident that these lipids or synthetic analogues have considerable therapeutic potential in managing chronic inflammatory diseases, including arthritis, cardiovascular disease, asthma and even cancer. From a nutritional or health standpoint, it has been suggested that dietary supplements of the precursor omega
-3 fatty acids, taken together with aspirin, may ameliorate the clinical symptoms of many inflammatory disorders by regulating the time course of resolution via the production of resolvins and protectins