Table 2.
Immunomodulatory effects of hydroxychloroquine (HCQ) and chloroquine (CQ) in multiple test systems
| Test systems | Drugs | Dose Range | Endpoints | Effects | References |
|---|---|---|---|---|---|
| Human lymphocytes in vitro (PBMC) | CQ | 0–25 μg/ml | Inhibition of generation of immunoglobulin-secreting cells and IL-1 secretion | + | [54] |
| Systemic Lupus Erythematosus Patients | HCQ | 400 mg/day for 12 weeks | Decreased levels of cytokines (IL-6), soluble CD8 and soluble IL-2 receptors | + | [55] |
| T-cell line | HCQ | 0–100 μM | Inhibits calcium signals in T cells | + | [18] |
| PBMC from healthy donors | CQ | 0–10 μM | Inhibition of RNA- mediated TLR7 activation; inhibition of IFN-α | + | [56] |
|
PBMC and monocytic U-937 and THP-1 cells in vitro |
CQ | 0–100 μM | Inhibition of cytokine (TNF-α, IL-1β and IL-6) production. | + | [57] |
| Macrophage-like RAW264 cells in vitro | CQ | 0–100 μM |
Inhibition of Toll-like Receptor (TLR) signaling pathways |
+ | [58] |
| Systemic Lupus Erythematosus Patients, Human embryonic kidney cells | CQ | 5–10 μg/ml | Inhibits activation of endosomal TLRs | + | [4] |
| Systemic Lupus Erythematosus Patients | HCQ | 200–400 mg/day | Impaired IFN-α and TNF-α production | + | [5] |
| Human lymphocytes in vitro (PBMC) | HCQ | 0–20 nmol/L |
Inhibition of autophagy, and induction of apoptosis of memory T-cells |
+ | [59] |
| MonoMac1 (MM1) cells, human monocytes | HCQ | 0–100 μM | Inhibits pro-inflammatory signaling pathways, prevents the induction of endosomal NADPH oxidase | + | [60] |
|
Systemic Lupus Erythematosus Patients and on Jurkat Cell |
HCQ |
Patients blood samples and in Jurkat cell 600–6000 ng/ml |
Inhibition of NFAT signaling in activated T cells and CD154 expression in CD4+T cells | + | [17] |
| A549Pt and A549cisR non-small-cell lung cancer cell lines | CQ | 25–100 μM | Lysosomal membrane destabilization and autophagy | + | [16] |
| PBMC from healthy volunteer | HCQ | Data not available | BlocksTLR9 ligation in class-switched memory B cells, suppress mTORC1 signaling. | + | [61] |
| Rosetta BL21 pLysS cells | HCQ and CQ | 1–4 μM | Blockade of c-GAS-DNA interaction | + | [62] |
+: positive effects, CQ: Chloroquine, HCQ: Hydroxychloroquine, IL: Interleukin,
TLR: Toll-like receptor, PBMC: Peripheral blood mononuclear cells,
TNF: Tumor necrosis factor; cGAS: Cyclic GMP-AMP synthase