Table 1.
Characteristics of the included studies
| Author first, last, year, journal | Species | Sex | Type of induction of disease | Aza or DAC | n/group | Dose | Dose regimen (frequency and timing) | Route of administration | Clinical outcome |
|---|---|---|---|---|---|---|---|---|---|
| Graft versus host disease (GvHD) | |||||||||
| Paluska Cihak 1982 Immunobiology* | Mice | M+F | Allogeneic splenocyte injection | Aza and DAC | 8–17 | 6 or 20 mg/kg | 24 h after splenocyte injection | IP | Decreased GvHD, depending on dosing |
| Sula, Cihak, 1987, Czech Med | Mice | Unknown | Allogeneic splenocyte injection | Aza and DAC | 5–10 | 5-25 mg/kg | Day -1, 0, 1, or 2 or multiple days | IP | Decreased GvHD, depending on dosing |
| Sánchez-Abarca, Pérez-simon, 2010, the american society of hematology | Mice | M+F | BM transplantation + allogeneic splenocyte injection | Aza | 5 | 1 mg/kg | after 60 and 84 h | IV | Decreased GvHD, increased survival |
| Choi, Dipersio, 2010, the american society of hematology | Mice | Unknown | BM transplantation + allogeneic T cell injection | Aza and DAC | 2–25 | DAC: 1mg/kg , Aza: 2 mg/kg | Day 4, 6, 8, 10 after T cells | SC or IP | Decreased GvHD, increased survival |
| Fransolet, Baron, 2016, Journal of hematology and oncology | Mice | M+F | BM transplantation + allogeneic splenocyte injection | Aza and DAC | 3–16 | DAC 0,75mg/kg, Aza 0,5 or 2 mg/kg | Day 10 2013Day 30, every 48 h | SC | Decreased GvHD, depending on dosing |
| Cooper, DiPersio, 2017, Journal of immunology | Mice | M | BM transplantation + allogeneic T cell injection | Aza | 3–10 | 2 mg/kg | Day 15, 17, 19 and 21 | IP | Decreased GvHD, this is Treg dependent |
| Ehx,Baron 2017 OncoImmunology | Mice | Unknown | Human PBMC injection (xeno–GvHD) | Aza | 8–12 | 2 or 5 mg/kg | Day 1 – Day 21, every 48h | SC | Decreased GvHD, increased survival |
| Organ rejection | |||||||||
| Paluska Cihak 1982 Immunobiology* | Mice + Rats | M+F | Skin transplantation | Aza and DAC | 4–11 | 6 or 20 mg/kg | Day -1, 1, 3, 5 | IP | Prolonged graft survival, depending on dosing |
| Cheng C, Xia J, 2014, Immunology | Mice | M# | Cardiac transplantation | Aza | 3–6 | 1 mg/kg | Daily untill end of exp. | IP | Aza alone did not prolong graft survival |
| Guo, Jiang, 2013, Transplant immunology | Mice | M | Cardiac transplantation | DAC | 6 | 1,5 mg/kg | Day 1,2 and 3 | IV | Prolonged graft survival |
| Wang X, Tao, 2017, Oncotarget^ | Mice | M | Cardiac transplantation | DAC | Unknown | 0,25 or 0,5 mg/kg | Daily for 14 days | IP | Prolonged graft survival |
| Uchida, Tisdale, 2014, PLOS ONE | Mice | M | Human stem cell transplantation (Xeno-rejection) | DAC | Unknown | 0,5 μM (ex vivo) | 48 h ex vivo prestimulation | Unknown | Prolonged graft survival |
| Hong J, Yang, 2013, Transplant immunology | Mice | Unknown | Islet transplantation | Aza | 6-9 | 1 mg/kg | Day 0 and 1 | Unknown | Aza alone did not prolong graft survival |
| Diabetes | |||||||||
| Zheng, Zhao, 2009, J mol med | Mice | M+F | NOD mice + cyclophosphamide injection | DAC | 5 | 0,1 or 0,15 mg/kg | Daily for 5 days or 5 weeks | IP | Prevented diabetes |
| Wang, Shi, 2016, JCI insight | Mice | M | ob/ob mice + high fat diet | DAC | 6–16 | 0,25 mg/kg | 3x/week for 8 weeks | IP | Improved insulin sensitivity |
| Gao, Mu, 2019, Stem Cell Research and Therapy | Mice | M | C57BL/6 mice + high fat diet + STZ | DAC | 18 | 0,25 mg/kg | Daily for 5 days | IP | DAC alone did not improve clinical outcome |
| Chen, Dong, 2019, Kidney international | Mice | M | db/db mice | DAC | 6-9 | 1 mg/kg | 2x/wk from week 8-20 | IP | Improved diabetic nephropathy |
| Zhang, Liang, 2017, Kidney International | Mice | M | db/db mice | Aza | 6 | 1 or 2 mg/kg | 3x/week for 8 weeks | IP | Improved diabetic nephropathy, no effect on blood glucose levels |
| Atherosclerosis | |||||||||
| Cao, Xua , 2014, Endocrinology | Mice | M | ldlr mice + High fat and cholesterol diet | DAC | 8 | 0,25 mg/kg | 3x/week up to 30 weeks | IP | Decreased Atherosclerosis Development |
| Biliary Arthresia | |||||||||
| Li, Tang, 2016, the american physiological society | Mice | M+F | IP RVV injection | Aza | 8–17 | 2,5 mg/kg | Day 1,2 and 3 | IP | Decreased biliary arthresia and increased survival |
| Systemic Lupus Erythematodes (SLE) | |||||||||
| Yoshida, Izni, 1990, European journal of immunology | Mice | F | MRL-lpr mice | Aza | 9–23 | 50 ug | 2x/week from 6–21 weeks | IP | Increased survival and clinical outcome |
| Mizugaki, Nose, 1997, Clin Exp Immunol | Mice | Unknown | MRL-lpr mice | Aza | 4–10 | 50 ug | 2x/week from 4–20 weeks | IP | Increased survival and clinical outcome |
| Li, Tsokos, 2018, JCI Insight | Mice | F | MRL-lpr mice | Aza | 4–6 | 5 μg (targeted to CD4+ cells) | every 10 days for 60 days | Unknown | Increased survival and clinical outcome in case of targeted delivery |
| Vitiligo | |||||||||
| Sreekumar, Smyth, 1996, Clin immunol immunopathol | Chicken | Unknown | Smyth line chicken | Aza | 5–16 | 1 or 3 mg/kg | every 3 days up to 18 weeks | IP | Prevention of vitiligo in 1 strain, no effect in the other strain |
| Acute Respiratory Distress Syndrome (ARDS) | |||||||||
| Huang, Wang, 2016, Biomedicine & Pharmacotherapy | Mice | M | IP injection of LPS | Aza and DAC | 8 | 1 mg/kg | 1 h before LPS | IP | Alleviated lung injury |
| Cui, Shang, 2019, Laboratory Investigation | Mice | M | Inhalation of LPS | Aza | 6–8 | 1 mg/kg | 1 h after LPS | IP | Alleviated lung injury |
| Singer, D'alessio, 2014, Am Journal of Respiratory Cell and Molecular Biology | Mice | M | Inhalation of LPS | DAC | 5–8 | 1 mg/kg | daily, starting 24 h after LPS | IP | Alleviated lung injury |
| Thangavel, Rajasingh, 2014, Am Journal of Pathology | Mice | M | IP injection of LPS | Aza | 3–5 | 4,4 μmol/L/kg | 1 h after LPS | IP | Aza alone did not increase survival |
| Thangavel, Rajasingh, 2015, Journal of Cell Science | Mice | M | IP injection of LPS | Aza | 5 | 1 mg/kg | 1 h after LPS | IP | Aza alone did not increase survival |
| Asthma | |||||||||
| Wu, Kuo, 2013, Allergy and Immunology | Mice | F | Injection and inhalation of ovalbumin | Aza | 4–11 | 10,50,100 μg/dose | Every 3 days before OVA challenge | IP | Decreased airway hypersensitivity |
| Brand, Renz, 2012, Journal of Allergy and Clinical Immunology | Mice | F | Injection and inhalation of ovalbumin | DAC | 4–6 | 0,2 mg/kg | Every 2 days before OVA challenge | IP | Decreased airway hypersensitivity |
| Rheumatoid Arthritis (RA) | |||||||||
| Kröger, Ehrlich, 1999, General Pharmacology | Rats | M | Injection of adjuvant in the paw | Aza | 3 | 25 mg/kg | Day 3, 5, 7, 11, 15 | IP | Aza partly seemed to decrease RA |
| Tóth, Rauch, 2019, Arthritis & Rheumatology | Mice | F | IP injection with proteoglycans | Aza | 3–12 | 2 mg/kg | Every 2 days for 2 or 4 weeks | IP | Decreased RA |
| Multiple Sclerosis (MS) | |||||||||
| Chan, Wu, 2014, Molecular medicine | Mice | F | Injection of mog and heat-killed m. Tuberculosis | Aza | 3–5 | 0,15 mg/kg/ | Daily from Day-5 untill Day 10 | IP | Protects against EAE |
| Wang X, Tao, 2017, Oncotarget ^ | Mice | M | Injection of mog and heat-killed m. Tuberculosis | DAC | 5 | 0,25 mg/kg | Daily from Day 3 or Day 10 | IP | Protects against EAE, both prevention and treatment protocol |
| Mangano, Nicoletti, 2014, Journal of Cellular Physiology | Mice | M+F | Injection of mog or plp and heat-killed m. Tuberculosis | DAC | 5–12 | 0,1 mg/kg | Daily from Day 0, Day 7 or from clinical onset | IP | Protects against EAE, both prevention and treatment protocol |
| Guillain Barré Syndrome (GBS) | |||||||||
| Fagone, Nicoletti, 2018, Journal of Neuroimmunology | Mice + Rats | M | Injection of p0 peptide and M. Tubercolosis | DAC | Unknown | 0,1 mg/kg | Daily from Day 5 or from clinical onset for 21 days | IP | Decreased EAN, both prevention and treatment protocol |
Two articles discuss different diseases and are therefore mentioned twice in the table. They are listed with * or ^
M male, F female, IP intraperitoneal, IV intravenous, SC subcutaneous, GvHD graft versus host disease, LPS lipopolysaccharides, OVA ovalbumin, MOG myelin oligodendrocyte glycoprotein, PLP proteolipid protein, EAE experimental autoimmune encephalomyelitis, EAN experimental autoimmune neuritis