Anthralin (dithranol) in vitro inhibits human monocytes to secrete IL-6, IL-8 and TNF-α, but not IL-1

Abstract

Anthralin is a most widely used compound for topical treatment of psoriasis. Whereas numerous studies have ascertained anthralin as a safe and effective drug its mode of action still remains unclear. Previous studies demonstrated dose-dependent inhibition of a number of pro-inflammatory functions in human neutrophils and monocytes (MO). The aim of the present study was to investigate in stimulated MO the effect of anthralin on the secretion of cytokines which are of known importance for the psoriatic tissue reaction. Highly purified MO were incubated with anthralin (0.01-1.0 microgram/ml), its clinically inactive derivative danthrone (0.1 and 10 micrograms/ml), the solvent acetone, or medium alone. Culture supernatants were analysed for immunoreactivity for interleukin-1 beta, and -8 (IL-1 beta, IL-8), and tumour necrosis factor alpha (TNF-alpha) by specific ELISA. IL-6 bioactivity was determined using the B9-bioassay. Additionally, IL-1 bioactivity was measured by the D10[N4]M-bioassay. The results show a dose-dependent inhibition of MO IL-6, IL-8, and TNF-alpha release with a half-maximal inhibitory concentration of 0.25-0.6 microgram/ml of anthralin. There was no effect of danthrone or acetone on the secretion of these cytokines from MO. Secretion of IL-1 beta immunoreactivity measured by ELISA as well as determination of biological activity of IL-1 using the D10[N4]M-bioassay revealed a slight increase in IL-1 secretion with a maximum at an anthralin concentration of 0.1 microgram/ml. Danthrone at a concentration of 10 micrograms/ml and acetone (0.1%) similarly enhanced IL-1 secretion from human MO measured by both methods. Our results demonstrate a differential, dose-dependent inhibition of cytokine secretion from human MO by anthralin. The present data provide evidence that the anti-inflammatory and anti-proliferative activity of anthralin may at least in part be due to its inhibitory effect on pro-inflammatory cytokine secretion by MO.

Anthralin/dithranol in dermatology

“…Anthralin inhibits human monocytes in vitro , 8 resulting in decreased levels of IL‐6, IL‐8, and TNF‐α but not IL‐1. The effects of dithranol on neutrophil superoxide generation in psoriatics have also been studied 9 .…”

“…Reports on the effect of topical corticosteroids on dithranol irritation are largely contradictory 83,85,86 . Some studies indicate that the addition of a topical corticosteroid reduces dithranol irritation, 8 while others are contradictory 86 . A 24‐hour pretreatment and 3‐day post‐treatment with clobetasol‐17‐propionate did not influence dithranol‐induced inflammation after a 2‐hour application of 10% dithranol in petrolatum 87 .…”

Antipsoriatic drug anthralin induces EGF receptor phosphorylation in keratinocytes: requirement for H2O2 generation

“…Numerous studies with conflicting results have attempted to investigate the mode of action of anthralin. Anthralin exerts antiproliferative (4) and anti‐inflammatory effects in psoriasis (5–7). It also activates NF‐κB, a central transcription factor of inflammatory and differentiation immune responses (NF‐κB) in keratinocytes (8) and induces an inflammatory reaction in normal skin (9).…”

Topical Anthralin Therapy for Refractory Nail Psoriasis

“…An immunosuppressive effect of anthralin has also been proposed (10). Mrowietz et al (15) showed that anthralin inhibits the secretion of interleukin-6 (IL-6), IL-8, and tumor necrosis factor a (TNF-a) from lipopolysaccharide (LPS)-stimulated human monocytes. Our result that anthralin is more effective on onycholysis and subunguial hyperkeratosis reflects the possibility that this drug may act mainly on the nail bed and hyponychium.…”