Table 2  Main mechanisms of action underlying biological effects of HCQ.
Disease  Experimental Model  Dosage  Mechanisms of Action  References
Rheumatoid arthritis (RA)  Preclinical  40 mg/kg/day  ↓neutrophil-derived oxidants ↓inflammation  [75]
Clinical (randomized double-blind, placebo-controlled trial)  7 mg/kg/day  ↓inflammation  [76]
Clinical (comparative randomized double-blind trial)  200–400 mg/day  ↓inflammation  [77,78]
RA-associated cardiovascular disease  Clinical  n.a.  ↓IL-6 and leptin↓dyslipidemia  [79]
Clinical (cohort study)  6.5 mg/kg/day  ↓triglycerides and LDL↓dyslipidemia  [80]
Clinical (randomized double-blind cross-over trial)  6.5 mg/kg/day  ↓cholesterol and LDL↓dyslipidemia  [81]
Clinical (cross-sectional observational study)  200 mg/kg/day  ↓fasting glucose  [82]
Systemic lupus erythematosus (SLE)  Clinical (randomized double-blind placebo-controlled trial)  100–400 mg/kg/day  ↓inflammation↓risk of exacerbations  [83]
Clinical (long-term randomized study)  272 mg/day  ↓inflammation↓risk of exacerbations  [84]
Clinical (case-control study)  6.5 mg/kg/day  ↓inflammation↑ survival  [85]
Preclinical  100 mg/kg/day  ↓Th17 response ↑Treg immunosuppressive effects  [86]
Clinical (prospective cohort study)  400 mg/day  ↓inflammatory markers  [87]
Clinical (multiethnic US cohort)  n.a.  ↓IFN-α  [88]
Preclinical  4–40 mg/kg/day  ↓ mast cells↓ skin lesion  [89]
SLE-associated cardiovascular disease  Preclinical  10 mg/kg/day  ↓ROS↓endothelial damage  [90]
Preclinical  3 mg/kg/day  ↓ROS and nitric oxide↓ endothelial damage  [91]
Clinical  400 mg/day  ↓triglycerides and LDL  [92]
Clinical (cross-sectional study)  400 mg/day  ↓ fasting glucose  [82]
SLE-associated pregnancy complications  Clinical (randomized double-blind)  n.a.  ↓inflammation  [93]
Clinical (prospective study)  6.5 mg/kg/day  ↓inflammation↓risk of exacerbations  [94]
Antiphospholipid syndrome  Preclinical  200 μg/day  ↓inflammation↓complement activation↓placental abnormalities  [95]
Clinical (case report)  400 mg/day  ↓vascular thrombosis  [96]
Preclinical  12 μg/g/day  ↓endothelial damage ↓nitric oxide synthase  [97]
Preclinical  20 mg/kg/day  ↓endothelial damage ↓nitric oxide synthase  [98]
Clinical (observational prospective study)  200 mg/day  ↓thrombotic events in patients ↓soluble tissue factor levels.  [99]
Sjögren syndrome  Clinical  200 mg/day  ↓inflammation ↓IgG and IgA  [100]
Clinical (prospective study)  400 mg/day  ↓xerostomia  [101]
Clinical (prospective study)  6.5 mg/kg  ↓eye dryness  [102]
Preclinical  50 mg/kg/day  ↓ xerostomia ↓ TGF-β↓inflammation  [103]
Preclinical  60 mg/kg/day  ↓inflammation↓lymphocytic infiltration  [104]
Diabetes  Preclinical  80–120–160 mg/kg/day  ↓blood glucose  [105]
Preclinical  200 mg/kg/day  ↓inflammatory markers↑metabolic profile  [106]
Clinical (randomized, double-blinded study)  2 × 300 mg/kg  ↓glycated hemoglobin  [107]
Clinical (open-label longitudinal study)  6.5 mg/kg/day  ↓insulin resistance  [108]
Clinical (randomized, double-blinded controlled trial)  6.5 mg/kg/day  ↓insulin resistance  [109]
Clinical (randomized, double-blinded trial)  400 mg/day  ↑glycemic and lipidic profile  [110]
Cancer  Preclinical  50 mg/kg  ↓tumor size↓pro-tumorigenic and pro-inflammatory cytokines  [111]
Cardiovascular diseases  Preclinical  200 mg/kg  ↓apoptosis in cardiomyocites  [112]
Preclinical  200 mg/kg/day  ↓triglycerides and LDL  [113]
Preclinical  10 mg/kg/day  ↓atherosclerosis↓inflammation  [114]
Inflammatory bowel disease and colitis  Preclinical  30 mg/kg  ↓inflammation  [74]
Pulmonary hypertension  Preclinical  50 mg/kg/day  ↓inflammation  [115]
Endometriosis  Preclinical  60 mg/kg  ↓inflammation↓lesion number  [116]
LDL: low-density lipoproteins, Th17: effector lymphocyte T, Treg: regulatory lymphocyte T, IFN-α: type I interferon, ROS: radical oxygen species, Ig: immunoglobulin, TGF-β: transforming growth factor-β; n.a.= data not available.