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Impaired recovery from peritoneal inflammation in a mouse model of mild dietary zinc restriction
Brett E Phillips1, Abby K Geletzke1, Philip B Smith2,3
1Departments of Surgery, Hershey, PA, USA.
Scope:
Mild dietary zinc (Zn) deficiency is wide-spread in human populations, but the effect on Zn-dependent processes of immune function and healing are not well understood. The consequences of mild dietary Zn restriction were examined in two mouse models of inflammation and recovery.
Methods And Results:
Male C57BL/6 mice were fed a Zn adequate diet (ZA, 30 mg Zn/kg diet), or diets containing sub-optimal Zn levels (ZM, 15 mg Zn/kg diet; ZD, 10 mg Zn/kg diet) for 30 days before a thioglycollate peritonitis challenge. Plasma lipid profiles were distinct, with greater Zn restriction resulting in a greater impact on metabolites. The milder ZM diet was selected for immune studies. Peritoneal macrophages from ZM mice displayed increased phagocytosis and amplified pro-inflammatory cytokine (IL-1β, IL-6, and TNFα) release compared to ZA, at baseline and after a secondary LPS challenge. Splenocytes isolated from ZM mice displayed an increase in IL-6 and a reduction in anti-inflammatory IL-4 compared to ZA. Cytokine levels in plasma were unaltered. Following mechanical manipulation of the intestines to induce ileus, ZM mice had delayed intestinal transit compared to ZA.
Conclusion:
Mild Zn deficiency enhances local inflammatory responses, amplifying macrophage functions and delaying recovery from acute insults within the peritoneum.
Insights
Mild zinc deficiency amplifies immune cell responses and impairs healing. This study shows that reduced zinc intake enhances macrophage activity and delays recovery from inflammation in mice.
Area of Science:
- Immunology
- Nutritional Science
- Cell Biology
Background:
- Mild dietary zinc deficiency is prevalent globally.
- Its impact on immune function and healing processes remains unclear.
Purpose of the Study:
- To investigate the effects of mild zinc restriction on immune responses and recovery.
- To examine zinc's role in inflammation and healing using mouse models.
Main Methods:
- Mice were fed zinc-adequate or zinc-restricted diets.
- Immune cell functions (macrophages, splenocytes) were assessed.
- Models of peritonitis and ileus were used to study inflammation and recovery.
Main Results:
- Zinc restriction altered plasma lipid profiles.
- Macrophages showed enhanced phagocytosis and pro-inflammatory cytokine release.
- Splenocytes exhibited altered cytokine profiles (increased IL-6, decreased IL-4).
- Ileus recovery was delayed in zinc-restricted mice.
Conclusions:
- Mild zinc deficiency potentiates local inflammatory responses.
- Enhanced macrophage function contributes to delayed healing.
- Dietary zinc is critical for effective immune response and recovery.
