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Protective effect of Flt3L on organ structure during advanced multiorgan dysfunction syndrome in mice
Guang Tian1, Jiangyang Lu1, Huiqin Guo2
1Department of Pathology, The First Affiliated Hospital of General Hospital of PLA, Beijing 100048, P.R. China.
Abstract:
The present study aimed to examine whether fms‑related tyrosine kinase 3 ligand (Flt3L) protects the organs of mice with multiorgan dysfunction syndrome (MODS). Male C57BL/6 mice were randomly assigned to normal control, MODS and Flt3L treatment groups. The mouse models of MODS were established using intraperitoneal zymosan injections, followed by normal saline injections. The treatment group received 5 µg/kg Flt3L for seven days, beginning on day five following zymosan injection. On day 12, the mortality rates of the Flt3L treatment and the MODS groups were 7 and 18%, respectively. Marked pathological changes were observed in the liver, lungs, kidneys and heart of the mice with MODS, including degeneration and focal necrosis of parenchyma cells. Mild pathological changes were observed in different organs of the Flt3L‑treated mice. In the MODS group, the number of CD4+ T lymphocytes was significantly reduced, whereas the number of CD8+ T lymphocytes was significantly increased compared with that in the normal control group; thus, the CD4+/CD8+ ratio was reduced. In the Flt3L treatment group, the average number of CD4+ T lymphocytes was not significantly different to the average number of CD4+ T lymphocytes in the normal group. In conclusion, Flt3L administration improved the immune status and alleviated the organ damage in mice with late‑phase MODS.
Insights
Fms-related tyrosine kinase 3 ligand (Flt3L) treatment reduced mortality and organ damage in mice with multiorgan dysfunction syndrome (MODS). Flt3L improved immune status, offering potential therapeutic benefits for MODS.
Area of Science:
- Immunology
- Pathology
- Pharmacology
Background:
- Multiorgan dysfunction syndrome (MODS) is a critical condition with high mortality.
- The role of immune dysregulation in MODS pathogenesis is increasingly recognized.
- Therapeutic strategies to modulate the immune response in MODS are needed.
Purpose of the Study:
- To investigate the protective effects of fms-related tyrosine kinase 3 ligand (Flt3L) in a mouse model of MODS.
- To evaluate the impact of Flt3L on organ damage and immune cell populations in MODS.
- To assess the potential of Flt3L as a therapeutic agent for late-phase MODS.
Main Methods:
- Male C57BL/6 mice were induced with MODS using zymosan injections.
- Flt3L (5 µg/kg) was administered to the treatment group from day 5 to day 12 post-induction.
- Mortality rates, pathological changes in major organs, and CD4+/CD8+ T-lymphocyte counts were assessed.
Main Results:
- Flt3L treatment significantly reduced mortality rates in MODS mice (7% vs 18%).
- Pathological damage in the liver, lungs, kidneys, and heart was significantly milder in Flt3L-treated mice compared to MODS controls.
- Flt3L administration helped restore the CD4+/CD8+ T-lymphocyte ratio towards normal levels.
Conclusions:
- Flt3L administration demonstrates protective effects against organ damage in late-phase MODS.
- Flt3L treatment improves immune status by modulating T-lymphocyte populations.
- Flt3L shows promise as a potential therapeutic intervention for MODS.
