Lipid-derived lipoxins are produced at the site of vascular and mucosal inflammation where they down-regulate polymorphonuclear leukocyte recruitment and function. 15(R)-Lipoxin A4 (15(R)-LXA4) is derived from the aspirin-triggered formation of 15(R)-HETE from arachidonic acid. [1] [2] 15(R)-LXA4 inhibits LTB4-induced chemotaxis, adherence, and transmigration of neutrophils with twice the potency of LXA4 demonstrating activity in the nM range.[2] [3] The anti-inflammatory effects of aspirin may be ascribed in part to the ability of 15(R)-LXA4 to regulate leukocyte function.[4] 15(R)-LXA4 is reported to promote resolution of inflammation in LPS-treated stromal cells derived from intermediate-stage diseased supraspinatus tendons as evidenced by increased expression of the STAT-6 pathway target genes, ALOX15 and CD206.[5]
Meclofenamate sodium is a potent non-steroidal anti-inflammatory agent, which can specifically inhibit chemokine-induced human polymorphonuclear leukocyte function: chemotaxis, degranulation, and superoxide anion free radical production.
Leukotriene B4 (LTB4) is a dihydroxy fatty acid derived from arachidonic acid through the 5-LO pathway. It promotes a number of leukocyte functions including aggregation, stimulation of ion fluxes, enhancement of lysosomal enzyme release, superoxide anion production, chemotaxis, and chemokinesis. 12-oxo LTB4 is an initial metabolite of LTB4 formed via the LTB4 12-hydroxydehydrogenase pathway. It is rapidly converted to 10,11-dihydro-12-oxo-LTB4, followed by reduction of the 12-oxo group to give 10,11-dihydro-LTB4. 12-oxo-LTB4 (EC50 = 33 nM) is about 70-fold less potent than LTB4 (EC50 = 0.46 nM) at stimulating Ca2+ mobilization in human neutrophils. It is also significantly less potent than LTB4 at stimulating neutrophil migration with EC50 values of 170 and 2.7 nM for 12-oxo-LTB4 and LTB4, respectively.