Multiple Sclerosis |
Experimental autoimmune encephalomyelitis (EAE) | C57BL/6 mice | P2X7 | oATP (5 or 10 mg/kg/day), Brilliant Blue G (5 or 10 mg/kg/day) | Attenuation of tissue damage and amelioration of neurologic consequences (increase in conduction latency) associated with EAE | Matute et al. (2007) |
C57BL/6 mice | P2Y12 | Clopidogrel (5, 15, 50 mg/kg/day), Ticagrelor (30 mg/kg/day) | Amelioration of clinical symptoms | Qin et al. (2017) |
Reduction of leukocyte infiltration in the spinal cord |
Inhibition of Th17 differentiation |
C57BL/6 mice | A2A | SCH58261 (2 mg/kg/day) | Protection of mice from EAE induction | Mills et al. (2008) |
C57BL/6 mice | A2A | CGS21680 (0.01 or 0.05 mg/kg/day) | Reduction of the severity of inflammation and tissue damage | Liu et al. (2016) |
Reduction of Th1, Th2, and Th17 cells and an increase in Treg cells, with the reduction of IFN-γ, IL-4, and IL-17 release and the induction of TGF-β release |
C57BL/6 mice | A2A | CGS-21680 (50 µg/kg/day) | Reduction of disease severity in EAE mice | Liu et al. (2018) |
Reduction of spinal cord CD45+ cells infiltration |
Decrease of blood-brain barrier permeability |
C57BL/6 mice | A2B | CVT-6883 (0.3, 1, 3 mg/kg/day), MRS-1754 (1 mg/kg/day) | Reduction of the peak severity and cumulative clinical score | Wei et al. (2013) |
Reduction of the percentage of Th17 and Th1 cells in the CD4+ population in the spleen |
Uveitis |
Immunization with the human interphotoreceptor retinoid-binding protein peptide IRBP1–20 | Female C57BL/6 (B6) mice | P2X7 | OxATP i.p. injection of 300 μg/mouse every 3 days | Reduction of Th17 autoreactive T cells | Zhao et al. (2016) |
Female C57BL/6 (B6) mice | Adenosine receptors | NECA i.p. injection of 100 ng/mouse | (0 days postimmunization) suppressive effect on disease development and Th17 responses | Liang et al. (2014) |
(7 days postimmunization) enhanced disease activity and Th17 responses |
C57BL/6 J mice | A2A | CGS 21680 0.5 mg/kg given i.p. once a day for 3 days | Administered at the peak of the disorder accelerated the resolution of disease | Lee et al. (2016) |
C57BL/6 mice | A3 | CF101 10 μg/kg p.o., twice daily for 19 days | Improvement of uveitis clinical scores, amelioration of the pathologic manifestations of the disease and reduction of antigen-specific proliferation and cytokine production of autoreactive T cells | Bar-Yehuda et al. (2011) |
Female C57BL/6 (B6) mice | Endogenous adenosine | ADA 5U/mouse given i.p. for 22 days | Suppression of the course of EAU when given 8–14 days post-immunization and augmentation when given either before or after this period | Liang et al. (2016b) |
Myasthenia gravis |
Immunization with AChR R97‐116 peptide | Female Lewis rats | A2A | CGS21680 0.5 mg/kg i.p. every 3 days for 29 days post EAMG induction | Amelioration of disease severity and decrease in the number of Th1 and Th2 cells while increasing the number of Treg cells | Li et al. (2012) |
Rheumatoid arthritis |
Freund’s adjuvant induced arthritis | DBA/1J mice | P2X7 | Suramin (30 mg/kg), A-438079 (5 mg/kg) | Attenuation of joint damage | Fan et al. (2016) |
Reduction of paw edema and IL-17 concentration in synovial fluid |
Collagen-induced arthritis | C57BL/6 mice | A2A (pro-drug) | 2-(cyclohexylethylthio)adenosine 5′-monophosphate (0.5 mg/kg/min) | Amelioration of clinical and histologic score | Flogel et al. (2012) |
Inhibition of proteo-glycan depletion and cartilage matrix erosion |
Reduction of IL-1, IL-6, IFN-γ, MCP-1, and TNF in synovial fluid |
Freund’s adjuvant-induced arthritis | Lewis rats | A3 | 1-(methylaminocarbonyl)bicyclo[3.1.0]hexane-2,3-diol] (also named CF 502) (1, 10, and 100 μg/kg) | Amelioration of clinical and histologic score | Ochaion et al. (2008) |
Reduction of PI3K, PKB/AKT, IKK, NF-κB, and TNF in paw extracts |
Reduction of GSK-3β, PARP, and β catenin in paw extracts |
Scleroderma |
Bleomycin-induced fibrosis | Male C57BL/6 mice | A2A | ZM241385 (50 mg/kg i.p. twice per day) | Attenuation of bleomycin-induced dermal fibrosis (reduced punch biopsy skin thickness, lower skinfold thickness) | Chan et al. (2006) |
Tcf/Lef:H2B-GFP mice | A2A | KW6002 (10 mg/kg once per day i.p) | Reduction of skin thickness, skinfold thickness, breaking tension, dermal hydroxyproline content, myofibroblast accumulation, and collagen alignment in bleomycin-induced dermal fibrosis | Zhang et al. (2017a) |
C57BL/6J mice and TSK1 mice | A2B | C57BL/6J mice: GS-6201 (p.o for 15 days) TSK1 mice: GS-6201(p.o for 30 days) | In C57BL/6J mice: reduction of dermal fibrosis and reduction of extracellular matrix molecule fibronectin and decreased number of alternatively activated macrophages | Karmouty-Quintana et al. (2018) |
In TSK1 mice: reduction of dermal fibrosis at the hyperdermal layer and reduction in hyperdermal layer thickness. |
Reduction of IL-6 and MCP-1 in the skin |
Psoriasis |
12-Otetradecanoylphorbol-13-acetate | Swiss CD-1 | A2A | CGS-21680 (5 µg per site) | Reduction of epidermal hyperplasia and promotion of collagen synthesis | Arasa et al. (2014) |
Normalization of epidermal structure and enhancement of fibroblast proliferation in the dermis |
Reduction of chemotactic mediator expression and Nfκ-B inhibition |
Systemic lupus erythematosus |
Genetic model | MRL/lpr mice | A2A | CGS-21680 (0.4 mg/kg per day, i.p. for 8 wk) | Reduction in proteinuria, blood urea, and creatinine as well as improvement in renal histology | Zhang et al. (2011) |
Reduction of renal macrophage and T-cell infiltration |
Reduction of MCP-1, IFN-γ and MHC-II expression |
Reduction of serum anti-dsDNA and renal immune complex deposition. Inhibition of NFκB activation and suppression the of IFN-γ, MCP-1 and MHC- II expression in splenocytes |
Glomerulonephritis |
Antibody-mediated glomerulonephritis | Male WKY rats | P2X7 | A-438079 (300 μmol/kg i.p. injection twice daily for 7 days) | Reduction in fibrinoid necrosis | Taylor et al. (2009) |
Reduction in proteinuria |
Reduction in glomerular macrophage infiltration |
Genetic model | MRL/lpr mice | P2X7 | brilliant blue G (45.5 mg/kg i.p. injection every 48 h for 8 wk) | Reduction of NLRP3/ASC/caspase 1 assembly, reduction of interleukin-1β release | Zhao et al. (2013) |
Reduction in the severity of nephritis and circulating anti-dsDNA antibodies. |
Reduction of the serum levels of IL-1β and IL-17 and in the Thl7:Treg cell ratio |
anti-GBM Ab | Male WKY rats | A2A | CGS 21680 1.5 mg/kg i.p. twice a day for 5 days | Reduction of damage to the kidneys | Garcia et al. (2008) |
Suppression of the glomerular expression of the MDC/CCL22 chemokine and down-regulation of MIP-1α/CCL3, RANTES/CCL5, MIP-1β/CCL4, and MCP-1/CCL2 chemokines |
Increase of anti-inflammatory cytokines, IL-4 and IL-10 |
Chronic obstructive pulmonary disease |
Smoke-induced lung inflammation | C57/Bl6 mice | P2X7 | KN62 (1 μM by mouth 30 min before each cigarette smoke exposure on days 1–3) | Prevention of the lung parenchyma destruction | Lucattelli et al. (2011) |
Asthma |
Ovalbumin | Balb/c and C57BL/6 mice | P2X4 | 5-BDBD (80 μl 100 μM, intratracheally before each of the three consecutive OVA-aerosol challenges) | Reduction of broncho alveolar lavage fluid eosinophilia, peribronchial inflammation, Th2 cytokine production and bronchial hyperresponsiveness | Zech et al. (2016) |
Balb/c and C57BL/6 mice | P2X7 | KN62 (10 μM, intratracheally before allergen challenge) | Reduction of airway eosinophilia, goblet cell hyperplasia, and bronchial hyperresponsiveness to methacholine | Muller et al. (2011) |
Reduction in allergic airway inflammation |
Balb/c and C57BL/6 mice | P2Y1 | MRS2179: 30 mg/kg, MRS2500: 3 mg/kg administered intravenously 20 min before the start of allergen challenge | Reduction of leukocyte recruitment to the lung | Amison et al. (2015) |
Female BALB/c mice | A2A | CGS-21680 (10 or 100 μg/kg intranasally, half an hour before and 3 h after the challenge) | Inhibition of bronchoalveolar lavage fluid inflammatory cell influx | Bonneau et al. (2006) |
No effect on OVA-induced bronchoconstriction |
Genetical model | ADA-deficient mice | A2B | CVT-6883 (1 mg/kg i.p. for 14 days) | Reduction of immune cell number in the BAL fluid, | Sun et al. (2006) |
Decreased production of pro-inflammatory cytokines and chemokines |
Attenuation of pulmonary fibrosis |
Inflammatory bowel diseases |
Trinitrobenzene sulfonic (TNBS) acid | Wistar rats | P2X7 | A740003 (16 mg/kg/day), Brilliant Blue G (40 mg/kg/day) | Amelioration of clinical and histologic scores | Marques et al. (2014) |
Reduction of macrophage and T-cell tissue infiltration |
Reduction of tissue apoptosis |
Inhibition of NF-kappa B and MAP kinase activation |
Spontaneous ileitis | SAMP1/YitFc mouse | A2A | ATL-146e (0.1 μg · kg−1 · min−1) | Decrease of the chronic inflammatory index and villus distortion index | Odashima et al. (2005) |
Reduction of TNF, IFN gamma, and IL- 4 in supernatants from cultures of mesenteric lymph node cells |
Oxazolone | Sprague-Dawley rats | A2A | PSB-0777 (0.4 mg/kg/day) | Amelioration of microscopic damage score | Antonioli et al. (2018a) |
Reduction of tissue TNF and oxidative stress |
Sodium dextran sulfate (DSS) | NMRI mice | A2A | CGS 21680 (0.5 mg/kg/day) | CGS 21680 was ineffective in ameliorating DSS-induced colitis in mice | Selmeczy et al. (2007) |
C57BL/6 mice | A2B | ATL-801 (10 mg/kg/day) | Reduction of clinical symptoms, histologic scores, IL-6 levels and proliferation indices | Kolachala et al. (2008a) |
Suppression of the inflammatory infiltrate into colonic mucosa and decrease of epithelial hyperplasia |
C57BL/6 mice | A2B | PSB1115 (1 mg/kg/day) | Increase in severity of DSS colitis | Frick et al. (2009) |
BALB/c mice | A3 | IB MECA (1 or 3 mg/kg/day b.i.d.) | Amelioration of clinical signs of colitis | Mabley et al. (2003) |
Reduction of tissue IL-1, IL-6, IL-12 MIP-1, MIP-2, MPO, and MDA levels |
Interleukin-10−/− | C57BL/6 mice | A3 | IB MECA (1 or 3 mg/kg/day b.i.d.) | Reduction of tissue IL-1, IL-6, MIP-1, MIP-2, MPO, and MDA levels | Mabley et al. (2003) |
Trinitrobenzene sulfonic (TNBS) acid | Sprague-Dawley rats | A3 | IB-MECA (1.5 mg/kg b.i.d.) | Improvement of the clinical and histologic score, appetite, and weight gain | Guzman et al. (2006) |
Reduction of free radical production |
Dinitrobenzene sulfonic (DNBS) acid | Sprague-Dawley rats | Adenosine deaminase | 4-amino-2-(2-hydroxy-1-decyl)pyrazole[3,4-d]pyrimidine (APP, 5, 15, or 45 micromol/kg) and erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride (EHNA, 10, 30, or 90 micromol/kg) | Amelioration of systemic (food intake, body and spleen weight) and colonic [macroscopic/microscopic damage, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and malondialdehyde (MDA)] inflammatory parameters | Antonioli et al. (2007) |
Antonioli et al. (2010a) |
interleukin-10−/− | C57BL/6 mice | Adenosine deaminase | Pentostatin (0.75 mg/kg) | Improvement of the clinical and histologic score | Brown et al. (2008a) |
Reduction of Th1 cytokines (IL-1β, IFN-γ, TNF, IL-6, CXCL10) |