Table 2.

DHA-derived SPM actions in disease models and cell targets.

SPM	Target	Bioaction	Reference
RvD1	Polymorphonuclear leukocyte	Decreases infiltration in murine skin air pouch model; limits infiltration in renal ischaemic injury	[36,42,43]
	Microglial cells	Inhibits IL-1β expression in vitro	[36]
	Vascular inflammation (arterial angioplasty)	Attenuates cell proliferation, leukocyte recruitment, and neointimal hyperplasia	[44]
	Alzheimer’s disease	Stimulates phagocytosis of Aβ by Alzheimer’s disease macrophages	[45]
	Pain	Controls inflammatory pain	[46]
AT-RvD1	Pain	Controls inflammatory pain	[47]
	Temporomandibular joint inflammation	Limits PMN infiltration to CFA-inflamed TMJ	[48]
	Arthritis	Antihyperalgesic	[49]
	Fibromyalgia	Reduces mechanical allodynia and thermal sensitization and prevents depressive behaviour	[50]
	Postsurgical cognitive decline	Improves postoperative decline and attenuates memory	[51]
PD1	Polymorphonuclear leukocyte	Upregulates CCR5 expression; reduces tissue infiltration	[52,53]
	Macrophages	Stimulates phagocytosis of apoptotic polymorphonuclear leukocyte	[54]
	T Cell	Promotes apoptosis in vitro	[55]
	Glial cells	Reduces cytokine production	[56]
	Epithelial cells	Protects from oxidative stress-induced apoptosis (retinal pigment epithelium)	[38]
	Eosinophils	Decreases recruitment in response to allergen	[57]
RvD2	Macroglia	Prohibits or reduces the activation of macroglia and microglia, respectively	[58]
	-	Downregulates TNF-α, IL-1β, iNOS, NF-k, NO, and ROS production	[35]
	Burn wound	Prevents secondary thrombosis and necrosis	[48]
RvD3 and AT-RvD3	Neutrophils	Regulates neutrophils and mediators, reducing murine peritonitis and dermal inflammation	[59]
RvD4	Protection and resolution of inflammation during bacterial infection	Stops leukocyte influx to the site of infection in the dorsal pouch cavity as well as the inflammation-initiating eicosanoids by reducing levels of PGD2 and LTB4	[60]
RvD5	Bacterial infection	Increases survival and lower antibiotic requirement	[48]
RvD6	Corneal nerve	Decreases inflammation and increases wound healing and nerve regeneration by decreasing the expression of the ACE2 receptor, furin, and integrins.	[61]
MaR1	Pain	Controls inflammatory pain	[37]
	Tissue regeneration	Promotes tissue regeneration in planaria	[37]
	Neuroprotection	Treats amyotrophic lateral sclerosis and spinal muscular atrophy Accelerates clearance of neutrophils and a reduction in macrophage accumulation at the lesion site	[62,63]
MaR2	Macrophage phagocytosis	Anti-inflammatory activity	[64]