Related Experiment Video
Updated: Jan 20, 2026
Author Spotlight: Development and Evaluation of a Cationic Nanoemulsion-Encapsulated Retinoic Acid System for Mucosal Vaccination
Published on: February 23, 2024
Retinoic acid modulates IL-4, IL-10 and MCP-1 pathways in immune mediated hepatitis and interrupts CD4+ T cells
Mahmoud Elshal1, Nashwa Abu-Elsaad1, Amr El-Karef2
1Pharmacology and Toxicology Dep. Faculty of Pharmacy, Mansoura University, Egypt.
Aims:
Immune mediated liver injury includes activation of different immune pathways that requires various modalities to control their consequences. The current study involves evaluation of retinoic acid (RA) modulatory effects on immune responses induced in concanavalin A (ConA) model of acute hepatitis.
Main Methods:
Mice were divided as follows: Control group; RA group: received 35 mg/kg RA; ConA group: received 15 mg/kg ConA; ConA + RA group: received ConA and RA as described. Liver function biomarkers were measured in addition to malondialdehyde as lipid peroxidation biomarker. Liver tissue sections were scored for necro-inflammation, neutrophils infiltration, CD4+ T cells infiltration and NF-κb positive cells. Effect on hepatic levels of TNF-α, IL-4, IL-10 and MCP-1 was evaluated as well.
Key Findings:
Injection of RA before ConA significantly (p < 0.001) decreased ALT, AST and LDH levels compared to their levels in ConA group. Hepatic infiltration of neutrophils and CD4+ T cells was markedly (p < 0.001) reduced by RA. Hepatic injury, necrosis and expression of NF-κb were significantly decreased by RA when injected before ConA challenge. A significant decrease in the measured cytokines TNF-α and IL-4 was observed in ConA + RA group in addition to a decrease in MCP-1 level. On the other hand, IL-10 was significantly increased in the latter group compared to ConA group.
Significance:
RA can protect against ConA-induced hepatitis through: interrupting early inflammatory response as neutrophils, monocytes and CD4+ T cells infiltration, modulating IL-4 level and subsequent production of TNF-α and NF-κb activation, mitigating second inflammatory responses through increasing IL-10 liver production.
Insights
Retinoic acid (RA) protects against concanavalin A (ConA)-induced hepatitis by reducing immune cell infiltration and inflammatory markers. RA treatment also modulates cytokine levels, increasing protective IL-10 and decreasing harmful TNF-α and IL-4.
Area of Science:
- Immunology
- Hepatology
- Pharmacology
Background:
- Immune-mediated liver injury involves complex immune pathways requiring targeted interventions.
- Acute hepatitis models, such as concanavalin A (ConA)-induced hepatitis, are crucial for studying liver inflammation.
- Modulating immune responses is key to managing liver damage.
Purpose of the Study:
- To evaluate the modulatory effects of retinoic acid (RA) on immune responses in a ConA-induced acute hepatitis model.
- To investigate RA's potential as a therapeutic agent for immune-mediated liver injury.
Main Methods:
- Mice were administered retinoic acid (RA) and/or concanavalin A (ConA).
- Liver function biomarkers (ALT, AST, LDH), lipid peroxidation (malondialdehyde), and hepatic immune cell infiltration (neutrophils, CD4+ T cells, NF-κb) were assessed.
- Hepatic levels of key cytokines (TNF-α, IL-4, IL-10, MCP-1) were quantified.
Main Results:
- RA significantly reduced liver injury biomarkers (ALT, AST, LDH) and lipid peroxidation in ConA-treated mice.
- RA markedly decreased hepatic infiltration of neutrophils, CD4+ T cells, and NF-κb positive cells.
- RA modulated cytokine profiles, decreasing TNF-α and IL-4 while significantly increasing IL-10.
Conclusions:
- Retinoic acid (RA) demonstrates protective effects against ConA-induced hepatitis.
- RA mitigates liver injury by interrupting early inflammatory cell infiltration and modulating key inflammatory mediators.
- RA's therapeutic potential lies in its ability to balance pro-inflammatory and anti-inflammatory cytokine responses.
More Related Videos
Related Concept Videos
01:40Cell-mediated Immune Responses
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
02:42Acidity of 1-Alkynes
The acidic strength of hydrocarbons follows the order: Alkynes > Alkenes > Alkanes. The strength of an acid is commonly expressed in units of pKa — the lower the pKa, the stronger the acid. Among the hydrocarbons, terminal alkynes have lower pKa values and are, therefore, more acidic. For example, the pKa values for ethane, ethene, and acetylene are 51, 44, and 25, respectively, as shown here.
01:29Amino Acid Biosynthetic Pathways
01:19Acid Halides to Alcohols: LiAlH4 Reduction
The mechanism proceeds in three steps. First, the nucleophilic hydride ion attacks the carbonyl carbon of the acid halide to form a tetrahedral intermediate. Next, the carbonyl group is re-formed, and the halide ion departs as a leaving group, generating an aldehyde. A second nucleophilic attack by the hydride yields an alkoxide ion, which, upon protonation, gives a primary alcohol as...
01:27C4 Pathway and CAM
C4 Pathway
The C4 pathway is used by plants such as...