Effectiveness and safety of a cream product containing zinc oxide for alleviating mosquito bite symptoms.

BACKGROUND: People frequently experience discomfort with immediate wheal, delayed papules, and pruritus from mosquito bites. A topical cream product containing zinc oxide is commercially available for the management of insect bites, but there has been no published evidence for its effectiveness and safety. AIMS: To evaluate the effectiveness and safety of this product in symptoms caused by mosquito bites. METHODS: An open-label, controlled study was performed on 41 healthy participants. All subjects received Aedes aegypti mosquito bites on the forearm. Then test product was randomly applied to the bitten areas of the left or right arm. The other arm was left untreated (control). The onset of pruritus relief was noted. The severity of pruritus was assessed using a visual analogue scale (VAS), ranging from 0 mm (no pruritus) to 100 mm (severe pruritus), and a 4-point pruritus score (0 = none; 1 = mild, not affecting normal activities; 2 = moderate, affecting normal activities to some extent; 3 = severe, significantly affecting activities) at four time points: 15 minutes after the mosquito bite (baseline), as well as 1 hour, 24 hours, and 48 hours after initiating treatment. The size of the bite reaction lesion was also measured at all time points. Any local cutaneous adverse reactions observed during the study were documented. RESULTS: The onset of pruritus relief in the treated group (25 ± 21.7 minutes) was significantly faster compared to the untreated group (118.7 ± 304.8 minutes). The reduction in VAS score at 1 hour was significantly greater in the product group (30.5 ± 16.22) compared to the control group (14.9 ± 9.9). Moreover, there was a significant difference in the reduction of pruritus score at 1 hour, with the product group (1.1 ± 0.5) showing a higher reduction compared to the control group (0.3 ± 0.4). However, there was no significant difference in the reduction of bite lesion size between the two groups. Throughout the study, no adverse events were reported. CONCLUSION: Our preliminary findings indicate that the product effectively reduces pruritus caused by mosquito bites but does not have a significant impact on the size of the bite lesions. The product was found to be safe and may be an option for managing mosquito bites pruritus.

Metformin inhibits IL-1ß secretion via impairment of NLRP3 inflammasome in keratinocytes: implications for preventing the development of psoriasis.

Psoriasis is a systemic inflammatory disease significantly associated with comorbidities including type 2 diabetes mellitus (T2DM). Metformin is utilized as a first-line agent for treating T2DM. Although metformin reportedly inhibits mature IL-1ß secretion via NLRP3 inflammasome in macrophages of T2DM patients, it remains unclear whether it affects skin inflammation in psoriasis. To test this, we analysed normal human epidermal keratinocytes (NHEKs), a major skin component, stimulated with the key mediators of psoriasis development, TNF-α and IL-17A. This stimulation induced the upregulation of pro-IL-1ß mRNA and protein levels, and subsequently mature IL-1ß secretion, which was inhibited by metformin treatment. To further reveal the mechanism involved, we examined how metformin treatment affected NLRP3 inflammasome activated by TNF-α and IL-17A stimulation. We found that this treatment downregulated caspase-1 expression, a key mediator of NLRP3 inflammasome. Furthermore, inhibitors of AMPK and SIRT1 abrogated the downregulation of caspase-1 induced by metformin treatment, indicating that AMPK and SIRT1 are essential for the inhibitory effect on NLRP3 inflammasome in NHEKs. As IL-1ß stimulation induced upregulation of IL-36γ, CXCL1, CXCL2, CCL20, S100A7, S100A8 and S100A9 mRNA and protein levels in NHEKs, we examined whether metformin treatment affects such gene expression. Metformin treatment inhibited upregulation of IL-36γ, CXCL1, CXCL2, CCL20, S100A7, S100A8 and S100A9 mRNA and protein levels induced by TNF-α and IL-17A stimulation. Finally, we examined whether metformin administration affected psoriasis development in an imiquimod-induced mouse psoriasis model. Oral metformin treatment significantly decreased ear thickness, epidermal hyperplasia and inflammatory cell infiltration. A cytokine profile in the epidermis under metformin treatment showed that IL-1ß, Cxcl1, Cxcl2, S100a7, S100a8 and S100A9 mRNA levels were downregulated compared with control levels. These results indicate that metformin administration prevented psoriasis development in vivo. Collectively, our findings suggest that metformin-mediated anti-psoriatic effects on the skin have the potential for treating psoriasis in T2DM patients.

Aryl Hydrocarbon Receptor Activation Downregulates IL-33 Expression in Keratinocytes via Ovo-Like 1.

BACKGROUND: IL-33, one of the IL-1 superfamily cytokines, has been shown to be associated with pruritus and inflammation in atopic dermatitis (AD). Furthermore, IL-33 production derived from keratinocytes reportedly has a crucial role in the development of AD; however, the mechanism of IL-33 expression has not been fully understood. METHODS: We analyzed IL-33 expression in normal human epidermal keratinocytes (NHEKs) treated with IL-4. RESULTS: IL-4 induced the upregulation of IL-33 expression in NHEKs. Based on the findings 1) that ovo-like 1 (OVOL1), a susceptible gene of AD, upregulates filaggrin (FLG) and loricrin (LOR) expression in NHEKs and 2) that reduced expression of FLG and LOR leads to production of IL-1 superfamily cytokines, we examined the involvement of OVOL1 in IL-33 expression in NHEKs. Knockdown of OVOL1 induced upregulation of IL-33 expression. Moreover, because Glyteer, an activator of aryl hydrocarbon receptor (AHR), reportedly upregulates OVOL1 expression, we examined whether treatment with Glyteer inhibited IL-33 expression in NHEKs. Treatment with Glyteer inhibited IL-4-induced upregulation of IL-33 expression, which was canceled by knockdown of either AHR or OVOL1. CONCLUSIONS: Activation of the AHR-OVOL1 axis inhibits IL-4-induced IL-33 expression, which could be beneficial for the treatment of AD.