Table 1.
In vivo approaches to induce resolution of inflammation
| Disease model | Drug | Effect on resolution | Refs. |
|---|---|---|---|
| Inhibition of leukocyte recruitment | |||
| Air pouch model in mice | AnxA1 of human neutrophil-derived microparticles | Decrease of leukocyte infiltration | Dalli et al (2008) |
| Rheumatoid arthritis in mice | LXA4 | Decrease of oedema, neutrophil influx, and mRNA levels of CXCL1, LTB4, and TNF after LXA4 treatment | Conte et al (2010) |
| Peritonitis in mice | Nanoparticles containing aspirin-triggered RvD1 or a lipoxinA4 analogue | Reduced neutrophil influx into the peritoneum, and resolution intervals | Norling et al (2011) |
| LPS-induced ALI | lactoferrin | Reduced lung neutrophil infiltration with less oedema and plasma leakage | Li et al (2012) |
| Air pouch and skin inflammation in mice | LXA4 analogue | Reduced neutrophil infiltration | Clish et al (1999) |
| Peritonitis in mice | RvE1 | Reduced leukocyte infiltration into the peritoneum | Arita et al (2005) |
| Colitis in mice | RvE1 | Increased survival rates, sustained body weight, improvement of histologic scores, reduced serum anti-2,4,6-trinitrobenzene sulfonic acid IgG and reduction of leukocyte infiltration and pro-inflammatory gene expression | Arita et al (2005) |
| Peritonitis in mice | Chemerin C15 | Reduction of neutrophil and monocyte infiltration into the peritoneum, enhancement of apoptotic cell phagocytosis of by macrophages and reduction of pro-inflammatory mediators | Cash et al (2008) |
| Induction of neutrophil apoptosis | |||
| Acute pleurisy, lung injury and arthritis in mice | R-roscovitine (CDK inhibitor) | Reduced presence of inflammatory cells (neutrophil and monocytes/macrophages) and amelioration of disease according to clinical scores | Rossi et al (2006) |
| Acute lung injury mice | 15-epi-LXA4 | Increased neutrophil apoptosis and efferocytosis | El Kebir et al (2009) |
| Lung inflammation in rats | Ectoine | Restoration of normal neutrophil apoptosis rates | (Sydlik et al 2013) |
| Pleurisy in rats | PD98059 (ERK inhibitor) | Decrease of total number macrophages and neutrophils in the pleural cavity, increased rate of neutrophil apoptosis | Sawatzky et al (2006) |
| Acute pleurisy in mice | Ac2-26 (AnxA1-active N-terminal peptide) | Reduction of neutrophils by induction of neutrophil apoptosis | Vago et al (2012) |
| Peritonitis in mice | Histone deacetylase inhibitors | AnxA1-dependent decrease in neutrophil, monocyte and macrophage infiltration | Montero-Melendez et al (2013) |
| Enhancement of efferocytosis and macrophage reprogramming | |||
| Microbial peritonitis/air pouch model in mice | RvD1, RvD5, PD1s | Enhancement of bacterial killing, neutrophil efferocytosis and prevention of hypothermia. Acceleration of resolution in combination with antibiotics | Chiang et al (2012) |
| Allergic airway inflammation model in mice | RvE1 | Suppression of the production of IL17, IL23 and IL6 and increased concentration of IFN-γ and LXA4 in brocheoalveolar lavage fluid, decrease of resolution intervals, acceleration of resolution of allergic airway pathology and hyper-responsiveness | Haworth et al (2008) |
| Sepsis model in rats | LXA4 | Increase of animal survival, decrease of blood bacterial load and pro-inflammatory mediators | Walker et al (2011) |
| Peritonitis in mice | RGD-AnxA5 | Enhancement of engulfment of apoptotic cells by macrophages and increase of secretion of IL-10 during efferocytosis | Schutters et al (2013) |
| CGD in mice | IFN-γ | Enhanced engulfment of apoptotic cells by macrophages | Fernandez-Boyanapalli et al (2010) |
| Peritonitis in CGD mice | IFN-γ | Enhanced engulfment of apoptotic cells by macrophages | Fernandez-Boyanapalli et al (2010) |
| Early renal fibrosis in rats | LXA4/benzoLXA4 | Prevention of collagen deposition and renal apoptosis. Inhibition of TNF production and stimulation of IL-10 | Borgeson et al (2011) |
| CGD in mice | IL4 | Normalized CGD macrophage efferocytosis | Fernandez-Boyanapalli et al (2009) |
| CGD in mice | PS | Restored IL4-dependent macrophage reprogramming and efferocytosis | Fernandez-Boyanapalli et al (2009) |
| Stimulation of tissue repair | |||
| Mucosal injury and ulceration in mice | AnxA1 | Promotion of intestinal epithelial migration trough activation of FPR1-, Rac1- and NOX1-dependent redox signalling to induce wound repair | Leoni et al (2013) |
| Rheumatoid arthritis model in mice | Flavopiridol (CDK inhibitor) | Suppression of synovial hyperplasia and joint destruction | Sekine et al (2008) |
| Rheumatoid arthritis model in mice | CDK4/6-selective inhibitor | Suppression of synovial hyperplasia and joint destruction | Sekine et al (2008) |
| Peritoneal and lung inflammation in mice | PS/PC liposomes | Induction of TGF-β secretion, resulting in accelerated resolution of inflammation | Huynh et al (2002) |
| Myocardial infarction in rats | PS/PC liposomes | Induction of angiogenesis, preservation of small scars, prevention of ventricular dilatation and remodelling | Harel-Adar et al (2011) |
| Retinal ischaemia in mice | PS/PC liposomes | Reduced expression of pro-inflammatory genes, reduced neuronal death in the retina after ischaemia-reperfusion | Dvoriantchikova et al (2009) |
| Liver cirrhosis in rats | Vitamin A-coupled liposomes carrying siRNAgp46 | Decrease in collagen recreation from HS cells and abrogation of hepatic stellate cells in fibrotic tissue through apoptosis, resulting in reduced fibrotic area in rat kidneys | Sato et al (2008) |
ALI, acute lung injury; Anx, annexin; CGD, chronic glomerular disease; LXA4, IFN, interferon; Lipoxin A4; PC, phosphatidylcholine; PS, phosphatidlyserine; Rv, resolving.