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The Iron Chelator and Anticancer Agent Dp44mT Relieves Allergic Inflammation in Mice With Allergic Rhinitis
Hee-Yun Kim1, Na-Ra Han1, Hyung-Min Kim2
1Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
Abstract:
Our previous study showed that an iron chelator and anticancer agent Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) has an antiinflammatory effect in human mast cells. However, antiinflammatory effect of Dp44mT remains unclear in animal models. In this study, we assessed whether administration of Dp44mT could relieve clinical symptoms of ovalbumin (OVA)-induced allergic rhinitis (AR) mice. After administration of Dp44mT, number of rubs was significantly decreased, and levels of histamine and IgE were suppressed in serum of AR mice. Also, serum levels of interleukin (IL)-1β, thymic stromal lymphopoietin (TSLP), and tumor necrosis factor (TNF)-α increased by OVA challenge were significantly lowered by administration of Dp44mT. T helper type 1 (Th1) cytokine interferon-γ level was significantly increased by administration of Dp44mT, whereas Th2 cytokines such as IL-4, IL-5, and IL-13 were significantly reduced by administration of Dp44mT. In intranasal tissues of AR mice, levels of IL-1β, TSLP, TNF-α, and IL-6 and activities and protein levels of caspase-1 were significantly reduced by administration of Dp44mT. Interestingly, administration of Dp44mT reduced number of infiltrated eosinophils and mast cells through the inhibition of macrophage inflammatory protein-2 and intercellular adhesion molecule-1 in intranasal tissues of AR mice. In conclusion, these results indicate that Dp44mT also has potential antiinflammatory effects in vivo as well as in vitro.
Insights
The anti-cancer drug Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) effectively reduced allergic rhinitis symptoms in mice. Dp44mT demonstrated significant anti-inflammatory effects by lowering key inflammatory markers and cell infiltration.
Area of Science:
- Immunology
- Pharmacology
- Allergy Research
Background:
- Previous research indicated the anti-inflammatory properties of Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) in human mast cells.
- The in vivo anti-inflammatory efficacy of Dp44mT, particularly in allergic rhinitis models, remained largely uninvestigated.
Purpose of the Study:
- To evaluate the therapeutic potential of Dp44mT in mitigating the clinical manifestations of ovalbumin (OVA)-induced allergic rhinitis (AR) in a murine model.
- To elucidate the underlying mechanisms by which Dp44mT exerts its anti-inflammatory effects in the context of AR.
Main Methods:
- Ovalbumin (OVA)-induced allergic rhinitis (AR) was established in mice.
- Mice were treated with Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT).
- Clinical symptoms, serum cytokine/chemokine levels, immunoglobulin E (IgE), histamine, and inflammatory cell infiltration in intranasal tissues were assessed.
Main Results:
- Dp44mT administration significantly decreased clinical signs of AR, including reduced rubbing behavior.
- Serum levels of histamine, IgE, IL-1β, TSLP, and TNF-α were significantly suppressed by Dp44mT.
- Dp44mT modulated T helper cell responses by increasing interferon-γ (Th1) and decreasing IL-4, IL-5, and IL-13 (Th2) cytokines, while also reducing intranasal inflammatory mediators and cell infiltration.
Conclusions:
- Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) demonstrates significant in vivo anti-inflammatory effects against allergic rhinitis in a mouse model.
- Dp44mT alleviates AR symptoms by suppressing key inflammatory cytokines, chemokines, and cellular infiltration.
- These findings suggest Dp44mT holds potential as a therapeutic agent for allergic rhinitis and related inflammatory conditions.
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