They are categorized as nonclassic eicosanoids and members of the specialized pro-resolving mediators (SPMs) family of polyunsaturated fatty acid (PUFA) metabolites.

Both responses are considered to be pro-inflammatory in that, while aimed at neutralizing invading pathogens and digesting foreign material, can contribute to damaging host tissues and thereby prolonging and promoting further inflammation.

Subsequent studies, however, found that these lipoxins, as well as their epimers, epi-LXA4 and LXB4, act primarily to dampen and resolve inflammation, i.e. they are anti-inflammatory cell signaling agents.

This step is catalyzed by enzymes with 15-lipoxygenase activity which in humans includes ALOX15, ALOX12, aspirin-treated cyclooxygenase 2, and cytochrome P450s of the microsomal, mitochondrial, or bacterial subclasses.

[4] In consequence of the operation of this anabolic pathway, LXs have very short half-lives in vivo, the epi-LXs have longer in vivo half-lives and thereby greater potencies than their LX epimers, and synthetic lipoxins that are metabolically resistant to this pathway have been prepared, used in animal models to study LX activities, and tested as potential therapeutic agents in animals and humans.

[5][7] Similar to various other AA metabolites such as LTA4 and 5-oxo-eicosatetraenoic acid, cells and tissues may convert LXs to 20-hydroxy products by omega oxidation; they also have been shown to ligate LXA4 to glutathione to form cysteinyl-lipoxins, initially LXC4, which is then sequentially metabolized to LXD4 and LXE4.

The consequential congregation of the various cell types promotes transcellular pathways in forming specialized pro-resolving mediators (SPMs), including the LXs, which then proceed to stimulate cellular and tissue responses that trend to reverse the actions of the pro-inflammatory mediators, dampen and reverse the inflammatory response, and initiate tissue repair.

ALX/FPR is a promiscuous (i.e. interacting with diverse ligands) receptor that binds and is activated by other ligands including: a) various N-formyl oligopeptides that, like FMLP, are either released by microbes and mitochondria or are analogs of those released by microbes and mitochondria; b) microbe-derived non-formyl oligopeptides; c) certain polypeptides that are associated with the development of chronic amyloidosis and/or inflammation including serum amyloid A (SAA) proteins, a 42-amino acid peptide form amyloid beta termed Aβ42, humanin, and a cleaved soluble fragment (amino acids 274–388) from the urokinase receptor; and d) other SPMs including resolvins RvD1, RvD2, RvD5, AT-RvD1, and RvD3 (see Specialized pro-resolving mediators).

[4] LXA4 and 15-epi-LXA4, when introduced by intrathecal administration into rodents, suppress the perception of inflammatory pain; this action may involve the ALX/FPR receptor shown to be present on the spinal astrocytes of test animal and, based on studies using 15-epi-LXA, inhibition of the NALP1 inflammasome signaling complex.

[19]) The ability of these LXs to block the actions of the three LTs may contribute to their ability to resolve allergic reactions; for example, LXA4 relaxes the smooth muscle contraction caused by the cysteinyl leukotrienes in the hamster cheek pouch assay and a metabolically resistant 15-epi-LXAA4 analog potently inhibits allergen-driven airway hypersensitivity and inflammation in a mouse model.

These genes include SOCS2 (i.e. suppressor of cytokine signaling 2), CYP1A1, CYP1A2, CYP1B1, glutathione S-transferase Ya subunit, quinone oxidoreductase, UDP-glucuronosyltransferase and aldehyde dehydrogenase 3 family, member A1.

LXA4 and ATLa were shown to activate transcriptional and functional (alkaline phosphatase and proliferation) responses via ERa in human endometrial epithelial cells in vitro and in mouse uterine tissue in vivo.

In a mouse model of endometriois physiologically relevant concentrations of ATLa caused a reduction in lesion size and impacted the production of inflammatory mediators.

Molecules regulated via ERa were also impacted, implying that Lipoxin A4 and analogues, inhibiting both proliferative and inflammatory pathways, might be considered as potential therapeutics.

[5][6][25] One or more of the lipoxins or their analogs have been demonstrated to suppress, limit severity, and/or increase survival in multiple inflammatory and allergic diseases in mouse and rat model studies.

[7][30] In a randomized controlled trial, topical application of 15-epi-LXA4 or a comparatively stable analog of LXB4, 15R/S-methyl-LXB4, reduced the severity of eczema in a study of 60 infants.