Chloroquine Enhances the Number of IL‐10 Producing Cells and the Expression of B7‐2 and ICAM‐1 in In Vitro‐Cultured PBMC

Abstract

Chloroquine is prescribed as both an anti-malarial and an anti-inflammatory drug. However, its immunomodulating effects remain largely unclear. Previous studies have shown that chloroquine inhibits antigeninduced proliferation, implying immuno-suppressive effects. In this study, we examined whether the inhibition of the proliferation reflects changes in the surface molecules that are important for T-cell activation and whether chloroquine affects the balance between pro-and anti-inflammatory cytokines. Chloroquine elevated the expression of the costimulatory and adhesion molecules B7-2 (CD86) and ICAM-1 (CD54) in peripheral mononuclear cells (PBMC). An increased percentage of CD14 cells was also observed, and within this cell population, an increase in ICAM-1 expression was revealed by double-staining experiments. Assessment of the frequencies of interleukin (IL)-10 and interferon (IFN)-g-producing cells in in vitro-cultivated PBMCs showed that the ratio between pro-and antiinflammatory cytokines changed after exposure to chloroquine, favouring anti-inflammatory immune responses. This effect was mainly because of increased frequencies of IL-10-producing cells and was seen with or without the presence of stimulating antigens or mitogens. Our findings indicate that chloroquine affects the direction of the lymphocyte stimulation towards an anti-inflammatory response by affecting the antigen-presenting cells (APC) and the balance between pro-and anti-inflammatory cytokines, rather than generally inhibiting cytokine production.

Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases

“…Hugosson et al (2002) found that CQ 10 or 30 lM reduced antigen-and mitogen-induced proliferation of PBMC, and that 10 lM CQ enhanced the number of IL-10 producing cells exposed to these stimuli. CQ had no effect on the number of TNF-a producing cells in PBMC exposed to these stimuli.…”

“…CQ had no effect on the number of TNF-a producing cells in PBMC exposed to these stimuli. CQ 10 lM increased the expression of the surface adhesion or reactive molecules, ICAM-1 (CD54), CD80 (137-1), CD86 (B7-2) and CD14 (Hugosson et al 2002). The enhanced expression of the anti-inflammatory cytokine, IL-10, by CQ may affect the balance of Th1/Tc1 and Th2/Tc2 cytokine responses.…”

Chloroquine Inhibits Ca2+ Signaling in Murine CD4+ Thymocytes

“…Previous studies have indicated that chloroquine and its analogs can block proliferative responses to T cell mitogens and alloantigens [6,9]. Furthermore, these drugs have been shown to inhibit the release of various pro-inflammatory cytokines, such as TNF-α and interleukin-6 (IL-6) [2,9,10]. These findings imply that chloroquine and its analogs can function as immunosuppressants by blocking one or more steps in the T cell activation pathway [6,9].…”

Reactive oxygen species mediate chloroquine‐induced expression of chemokines by human astroglial cells

“…Chloroquine was found to inhibit TNF-␣ production from human PBMC stimulated with fungus by alkaliz-ing the fungal phagosome (Weber and Levitz, 2001). Furthermore, chloroquine affects the balance between Th1 and Th2 cytokine expression by enhancing interleukin (IL)-10 production by PBMC (Hugosson et al, 2002). It has recently been shown that chloroquine inhibits the Raf-MEK-ERK pathway, which in part may be responsible for the anti-inflammatory effects of chloroquine (Weber et al, 2002).…”