Table 3. Roles for SPMs in non-pulmonary settings.

PowerPoint slide

Disease or procedure	Mediator	Role	Refs
Murine models of organ transplantation	Lipoxins	Lipoxin analogue and increased LXA4 receptor expression prolong orthotopic heart transplant survival	169
		Lipoxin prevents acute rejection after liver transplantation	170
	Resolvins	RvE1 prolongs survival of vascularized renal transplant	169
		RvD1 analogue prolongs corneal transplant survival	171
Graft versus host disease	Lipoxins	LXA4 and 15-epi-LXA4 administration improves clinical symptoms	172
Alzheimer disease	Lipoxins	LXA4 decreases NF-κB expression and recruits microglia, promoting clearance of amyloid-β deposits and improving cognition in mouse models	173
	Protectins	NPD1 promotes brain cell survival and an anti-apoptotic gene expression programme in human tissue	174
	Resolvins	RvD1 stimulates macrophage phagocytosis of amyloid-β in vitro in PBMCs from patients with Alzheimer disease	175
Amyotrophic lateral sclerosis	Resolvins	RvD1 inhibits IL-6 and TNF production in macrophages derived from post mortem samples	176
Murine models of inflammatory bowel disease or colitis	Lipoxins	15-epi-LXA4 enhances phagocytic clearance of bacteria and limits the inflammatory cytokine milieu	177
		LXA4, through NF-κB, downregulates pro-inflammatory cytokines and improves mortality	178
	Resolvins	RvE1 suppresses pro-inflammatory response of macrophages	179
		RvE1 blocks leukocyte inflammation and protects against colitis	157
		RvD2 and AT-RvD1 decrease neutrophil infiltration and cytokine response, and improves clinical metrics	180
Diabetes	Resolvins	RvD1 improves glucose tolerance and insulin sensitivity associated with obesity-induced diabetes in mice	181
		The RvD1 precursor 17-HDHA reduces adipose tissue inflammation and improves glucose tolerance in mouse models	182
Chronic pancreatitis	Resolvins	RvD1 limits inflammation in the dorsal horn, limiting allodynia in rat models	183
Murine models of corneal healing	Lipoxins	LXA4 and protectin D1 improve corneal healing and limit tissue injury	184
	Resolvins	RvE1 limits goblet cell loss in chronic dry eye	185
		RvE1 improves goblet cell function and tear formation and limits inflammation	186,187,188
Retinopathy	Resolvin and protectins	RvD1, RvE1 and protectin D1 all protect against revascularization in mouse models	189
Glomerulonephritis	Lipoxins	Lipoxin upregulation promotes preservation of function in experimental glomerulonephritis	190
Renal fibrosis	Lipoxins	LXA4 limits collagen deposition and promotes IL-10 while inhibiting pro-inflammatory cytokines in rat models	191
	Resolvins	In mouse models of ischaemia–reperfusion injury, RvD1 restores function, reduces infiltration of leukocytes and blocks macrophage activation	160
		RvE1 inhibits fibroblast proliferation in mouse post-obstruction injury models	192
	Protectins	In ischaemia–reperfusion injury, protectin D1 restores function, reduces infiltration of leukocytes and blocks macrophage activation	160
Arthritis	Lipoxins	LXA4 resolves inflammation mediated by PGE2 in mouse models of autoimmune arthritis	52
		LXA4 receptor agonist decreases histological joint destruction and decreases clinical severity in murine collagen-induced arthritis	193
	Resolvins	RvD1 and AT-RvD1 improves hyperalgesia through modulation of NF-κB and COX2 in dorsal root ganglia in rat models of arthritis	194
Cardiac reperfusion injury	Resolvins	RvE1 is cardioprotective and limits infarct size in rat cardiac ischaemia models	195
Atherosclerosis	Lipoxins	Overexpression of 15-lipoxygenase protects against lipid deposition and limits plaque development in rabbit transgenic models	196
Ischaemic stroke	Resolvins	AT-Resolvins are neuroprotective and limit leukocyte infiltration in mouse stroke models	197
Atopic dermatitis	Resolvins	RvE1 improves skin lesions through reduction of IL-4, IFNγ and eosinophill infiltration in murine models	198
Fibromyalgia	Resolvins	RvD2 and AT-RvD1 inhibit allodynia and limit depressive symptoms in a mouse disease model	199
Inflammatory pain in murine models	Resolvins	RvD1 limits pain and reverse thermal and mechanical injury in inflamed tissue	200
		RvE1 limits inflammation, as well as heat and mechanical pain	128
	Protectins	Protectin D1 inhibits capsaicin-induced TRPV1 currents and TNF-dependent pain hypersensitivity	125
	Maresins	MaR1 inhibits capsaicin-induced TPRV currents and reduces inflammation and chemotherapy-induced pain	127

17-HDHA, 17-hydroxy docosahexaenoic acid; AT, aspirin-triggered; COX2, cyclooxygenase 2; IFNγ, interferon-γ; IL-4, interleukin-4; LXA₄, lipoxin A₄; MaR1, maresin 1; NF-κB, nuclear factor-κB; NPD1, neuroprotectin D1; PBMC, peripheral blood mononuclear cell; PGE₂, prostaglandin E₂; RvD, resolvin D; RvE1, resolvin E1; SPM, specialized pro-resolving mediator; TNF, tumour necrosis factor; TRPV, transient receptor potential cation channel subfamily V.