Treatment effect of topical 4'4 diamino diphenyl sulfone (dapsone) gel on the mouse psoriasis model

Introduction and Aim: Psoriasis is a chronic inflammatory skin disease with a prevalence of 2% in the general population, with genetic and environmental factors playing a role in its aetiology. Topical and systemic treatments and phototherapy are used in the treatment of psoriasis. Dapsone (4,4'-diaminodiphenylsulfone) is a sulfone compound synthesised in the 1940s that has anti-inflammatory and antimicrobial properties. Due to its anti-inflammatory effects, it has been tried in limited cases of pustular psoriasis and has mostly been beneficial in these cases. In this study, we aimed to compare the efficacy of topical dapsone with topical corticosteroids in a murine psoriasis model in terms of clinical, histopathological and cytokine levels by ELISA. Materials and Methods: A total of 40 Balb/c mice (20 male and 20 female) with an average age of 6-8 weeks and body weight between 32-33 grams were used as experimental material. All animals were divided into 5 equal groups with 4 males and 4 females in each group. Topical creams were applied to the back and ear skin. The dorsal region was shaved under ketamine and xylazine anaesthesia and the initial ear thickness was measured. The first group received only imiquimod cream (Aldara) at a dose of 62.5 mg for 14 days. The second, third and fourth groups received only imiquimod cream (Aldara) at a dose of 62.5 mg for 7 days. After the seventh day, imiquimod cream was first applied to the same area, followed 6 hours later by dapsone gel (Acnewell) at a dose of 62.5 mg/kg in the second group, dapsone gel (Acnewell) at a dose of 125 mg/kg in the third group and betamethasone valerate cream (Betnovate) at a dose of 50 mg in the fourth group. The fifth group received topical application of diethylene glycol monoethyl ether (Merck), used as a solvent in Acnewell gel, for 14 days. On the seventh day, only clinical evaluation was performed. On day 14, after the clinical evaluation, the mice were euthanised under anaesthesia and skin samples were taken from the dorsal skin with a scalpel for histopathological evaluation and cytokine measurements. The results were compared between groups. Results: When the experimental groups were analysed in terms of weight and sex distribution, no significant difference was found between the groups (p>0.05). When the changes in ear thickness were analysed, significant differences were found between day 0 and day 14 in all groups (p<0.05). When analysing the changes in psoriasis area severity scores (PASI), significant differences were found between day 0 and day 7 in all groups, while significant differences were found between day 7 and day 14 in all groups except the first group (p<0.05). Histopathological evaluation on day 14 at the end of the experiment showed significant differences between groups in all parameters except Kogoj pustules and Munro microabscesses (p<0.05). On histopathological examination, the mean total histopathological scores of the high dose (125 mg/kg) dapsone and betamethasone valerate groups were close to each other. When cytokines were measured by ELISA, significant differences were found between the groups for all three cytokine levels (TNF-α, IL-17A and IL-23A). The differences were mainly due to the fifth group using diethylene glycol monoethyl ether. Discussion and Conclusion: There were no animal losses at the end of the study. When ear thickness measurements, psoriasis area severity score (PASI) and histopathological evaluation were analysed, the high dose (125 mg/kg) dapsone group achieved similar results to the betamethasone valerate group. Low-dose (62.5 mg/kg) dapsone treatment was less successful than high-dose (125 mg/kg) dapsone treatment in terms of clinical and histopathological improvement. This showed that the success of topical dapsone treatment was dose dependent. When cytokine levels (TNF-α, IL-17A and IL-23A) measured by ELISA were analysed, it was found that both groups treated with dapsone had similar cytokine levels to the first group treated with imiquimod alone. This showed that topical dapsone treatment had a weak effect on TNF-α, IL-17A and IL-23A cytokine levels. In conclusion, although topical dapsone treatment was found to be effective and safe in the murine psoriasis model, further phase studies are needed to find out whether it will have the same effect in humans.