Table 2.
Overview of experimental findings from studies on SPMs tested in different preclinical inflammatory disease models
| SPM type | Dosage | Route | Disease/in-vivo model | Outcome | Reference |
|---|---|---|---|---|---|
| Lipoxins | A. LXA4 5 μg per kg body weight | A. Intraperitoneal | A. Endometriosis surgically induced female C57BL/6J mice model | A. LXA4 treatment showed an effect on disease progression by attenuating pro-inflammatory and angiogenic mediators, matrix remodeling enzymes, estrogen metabolism, and signaling, as well as downstream proliferative pathways | A. [73] |
| B. ATL 1 μg per mouse | B. Intravenous | B. Murine melanoma model Male C57BL/6 mice | B. Treatment with ATL diminished the population of Ly6Chi monocytes in spleen, blood, and bone marrow, which decreased macrophage infiltration into the tumor and reduced the expression of the M2 marker on tumor-associated macrophages (TAMs) | B. [33] | |
| Resolvin D series | A. RvD1 5 μg per kg body weight | A. Intravenous | A. Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)/Experimental autoimmune neuritis (EAN) model male Lewis rats | A. RvD1 promoted macrophage phagocytosis of apoptotic T cells in the peripheral nervous system (PNS). Increased anti-inflammatory macrophage counts in PNS, upregulated TGFβ−1 by macrophages and increased total Treg cell counts | A. [82] |
| B. RvD1 20 ng per mouse | B. Intraplantar injection | B. Inflammatory model (CFA-induced hindpaw inflammation) Male Wistar rats | B. RvD1 did not stimulate neutrophils or macrophages | B. [94] | |
| C. RvD1 or AT-RvD1 1, 10 or 100 ng per mouse | C. Intravenous | C. Asthma FVB male mice | C. Relative to RvD1, AT-RvD1 resisted metabolic inactivation by macrophages and significantly enhanced macrophage phagocytosis in in vitro and in vivo, a new pro-resolving mechanism for the clearance of allergen from the airways | C. [113] | |
| D. RvD1 0–1000 ng, 100, 500, and 1000 ng per mouse | D. Intraperitoneal | D. Collagen antibody-induced arthritis (CAIA) model Female DBA/1J mice | D. RvD1 did not affect murine RAW 264.7 macrophage viability. It reduced TNF-α, IL-1 β, IFN-γ, PGE 2, and receptor activator of nuclear factor κ B (RANK) and concurrently enhanced IL-10 | D. [6] | |
| Resolvin E series | RvE1 50 ng per mouse | Intraperitoneal | Osteolysis model C57BL/6 mice | RvE1 significantly reduced inflammatory bone resorption by downregulating osteoclast differentiation mediated by differential regulation of NFκB and PI3K-AKT pathways | [43] |
| Resolvin T series | RvT1–4500 ng per mouse | Intraperitoneal | Murine E coli infectious inflammation model | RvT treatment limited further neutrophil recruitment to sites of inflammation and also reduced systemic inflammation, as demonstrated by reduced platelet-leukocyte aggregates. RvT-treated mice showed a reduction in TxB2, PGD2, and PGE2 and significantly increased exudate macrophage efferocytosis | [30, 31] |
| Protectins | A. PDX 300 ng and 1000 ng per mouse | A. Intraperitoneal | A. Sepsis Male C57BL/6 mice | A. PDX promoted M2 polarization, enhanced phagocytotic activity of macrophage, and accelerated resolution of inflammation, finally leading to the increased survival rate of septic mice | A. [152] |
| B.NPD1 50 ng (50 μl) per wound | B. Intradermal injection | B. Diabetic mouse model type 2 diabetic db/db and non-diabetic db/+ female mice | B. NPD1 appeared to be a macrophage produced factor that accelerated diabetic wound healing and promoted macrophage pro-healing functions in diabetic wounds | B. [59] | |
| Maresins | A. MaR1 2 μg per ml (50 μl), 100 ng per mouse | A. Intraperitoneal | A. Postoperative neuroinflammation Adult male C57BL/6 mice | A. MaR1 exerted distinct anti-inflammatory and pro-resolving effects through regulation of macrophage infiltration, NF-κB signaling, and cytokine release after surgery | A. [154] |
| B. MaR1 and RvD2 100 ng each per mouse | B. Intraperitoneal | B. Atheroprogression C57Bl/6 mice | B. MaR1 and RvD2 induced a shift in macrophage profile towards a reparative phenotype, which stimulated collagen synthesis in smooth muscle cells | B. [145] |
LXA4 lipoxin A4, ATL aspirin-triggered 15-epi-lipoxin A4, RvD1–5 resolvin D series, AT-RvD1 aspirin-triggered epimer resolvin D1, RvE1–2 resolvin E series, RvT1–4 resolvin T series, PDX protectin DX, NPD1 neuroprotectin D1, MaR1 maresin 1, TAM tumor-associated macrophages, AIDP acute inflammatory demyelinating polyradiculoneuropathy, EAN experimental autoimmune neuritis, PNS peripheral nervous system, TGFβ-1 transforming growth factor beta 1, Treg T regulatory cells, CFA complete Freund’s adjuvant, CAIA collagen antibody-induced arthritis, TNF-α tumor necrosis factor alpha, IL-1 β interleukin 1 beta, IFN-γ interferon gamma, PGE2 prostaglandin E2, TxB2, thromboxane B2, PGD2 prostaglandin D2, RANK receptor activator of nuclear factor κ B, IL-10 interleukin 10, NFkB nuclear factor kappa-light-chain-enhancer of activated B cells, PI3K-AKT phosphatidylinositol 3-kinase and protein kinase B