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Niclosamide Modulates the Cellular and Humoral Immune Response in Balb/c Mice
Bilal Mahmood Beg1, Aqeel Javeed1, Muhammad Ashraf1
1Department of Pharmacology & Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan.
Background:
Niclosamide, a STAT3 inhibitor, is widely under investigation due to its anti-cancer properties. STAT3 also exhibits an exciting role in the immune responses.
Objective:
This study aimed to evaluate the impact of niclosamide on immune response of mice.
Methods:
Niclosamide was administered to balb/c mice. To evaluate cell-mediated immune response, a contact-hypersensitivity (CHS) test, cyclophosphamide-induced neutropenic assay, and carbon clearance test were performed, whereas a humoral immune response was evaluated by hemagglutination assay (HA) and mice lethality test. The concentration of TGF-β1 was determined by enzyme-linked immunosorbent assay (ELISA) on murine peritoneal macrophages.
Results:
In the CHS test, niclosamide caused a decrease in skin thickness, significantly exhibiting a decrease in inflammation. A highly significant decrease in overall leukocyte count (lymphocytes and neutrophils) was observed before and after cyclophosphamide injection as compared with the control group. However, only a highly significant decrease in the neutrophil percentage was observed. Niclosamide has decreased the phagocytic process immensely compared with the control. In the HA titer, niclosamide was found to reduce the antibodies' titer compared with the negative control group. In the mice lethality test, the treatment groups have shown an increase in the percentage of mortality. TGF-β1 elevated in peritoneal macrophages when treated with niclosamide, in a dose-dependent manner.
Conclusion:
Niclosamide exerts potent immunomodulatory effects by significantly suppressing cell-mediated and humoral immune responses and increasing the levels of TGF-β1 in mice. Niclosamide might be added as an adjuvant to immunosuppressive drugs for the treatment of autoimmune diseases.
Insights
Niclosamide, a STAT3 inhibitor, suppresses key immune responses in mice, including cell-mediated and humoral immunity. This immunomodulatory effect, alongside increased TGF-β1, suggests potential for autoimmune disease treatment.
Area of Science:
- Immunology
- Pharmacology
Background:
- Niclosamide is a STAT3 inhibitor investigated for anti-cancer properties.
- STAT3 plays a significant role in immune responses.
Purpose of the Study:
- To evaluate the impact of niclosamide on the immune response in mice.
Main Methods:
- Administered niclosamide to balb/c mice.
- Assessed cell-mediated immunity via contact-hypersensitivity (CHS) test, cyclophosphamide-induced neutropenic assay, and carbon clearance test.
- Evaluated humoral immunity using hemagglutination assay (HA) and mice lethality test.
- Measured TGF-β1 concentration using ELISA on murine peritoneal macrophages.
Main Results:
- Niclosamide decreased skin thickness and inflammation in the CHS test.
- Observed significant reductions in leukocyte and neutrophil counts.
- Reduced phagocytic activity and antibody titers.
- Increased mortality in mice and elevated TGF-β1 levels in a dose-dependent manner.
Conclusions:
- Niclosamide exhibits potent immunomodulatory effects, suppressing cell-mediated and humoral immunity.
- Increased TGF-β1 levels were observed in niclosamide-treated mice.
- Niclosamide may serve as an adjuvant for immunosuppressive therapy in autoimmune diseases.
