Anthralin (dithranol)in vitroinhibits 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.

Antioxidants attenuate anthralin-induced skin inflammation in BALB/c mice: role of specific proinflammatory cytokines

“…Early, extracellular control of GM-CSF and TNF-␣ induction may provide a temporal advantage in amplifying the bioactivities of subsequently expressed chemokines and infiltrating leukocytes. Anthralin has also been reported to reduce the secretion of LPS-induced cytokine release by monocytes, including IL-6, IL-8, and TNF-␣ [33], although the significance of this observation is unclear.…”

Alteration of the Expression of Bcl-2, Bcl-x, Bax, Fas, and Fas Ligand in the Involved Skin of Psoriasis vulgaris following Topical Anthralin Therapy

“…Also, anthralin suppresses transcription of transforming growth factor-· mRNA in keratinocytes, as well as decreases epidermal growth factor receptor binding by reducing affinity of this receptor for its ligand [26]. Moreover, an immunosuppressive effect of anthralin has recently been proposed, such as inhibition of the secretion of interleukin-6 (IL-6), IL-8, and tumor necrosis factor-· from lipopolysaccharide-stimulated human monocytes [12]. Anthralin has recently been shown to exert a potent effect on keratinocytes and mononuclear cells through strong induction of lipid peroxidation and JNK activation [27].…”

“…Anthralin inhibits keratinocyte hyperproliferation and granulocyte function [7,11,12]. Although the mode of action of anthralin is not completely clear, it is reported that anthralin is susceptible to rapid photo-or autooxidation, generating secondary reactive oxygen species, which are supposed to inhibit cell proliferation [10].…”

“…Anthralin is susceptible to rapid photoor auto-oxidation, forming anthraquinones, anthralin dimers, and other persistent free radical products [6,7], which mediates several biologic responses including inhibition of cell proliferation [8][9][10]. Although anthralin exhibits both antiproliferative and anti-inflammatory effects in psoriasis [7,11,12], the mechanism of effectiveness of anthralin has not been completely elucidated as yet.…”

Dose-Dependent Inhibition of Ribonuclease P Activity by Anthralin

“…Despite a large number of clinical and experimental data the mode of therapeutic action of anthralin in psoriasis is still poorly understood. Various investigators have shown that anthralin inhibits key enzymes of metabolic pathways, cellular respiration and DNA synthesis [3] and exerts distinct immunomodulatory effects [4,5].…”