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Overproduction of monokines by leukocytes after stimulation with lipopolysaccharide in the elderly
Philip Gabriel1, Irem Cakman, Lothar Rink
1Institute of Immunology and Transfusion Medicine, University of Luebeck School of Medicine, Ratzburger Allee 160, 23538 Luebeck, Germany.
Abstract:
The elderly suffer from an impaired immune function being obvious in a higher susceptibility to infections. Especially the rate of complications after infection with Salmonella, normally confined to the gastrointestinal tract, is raised. We compared in a whole blood assay and in vitro stimulation of peripheral blood mononuclear cell (PBMC) the secretion of interleukin (IL)-1-beta, IL-6, IL-8 and TNF-alpha, after stimulation with lipopolysaccharid (LPS) from Salmonella abortus equi and Escherichia coli, phytohaemagglutinin (PHA) and toxic shock syndrome toxin-1 (TSST-1) by leukocytes of healthy young donors, healthy elderly and healthy elderly fulfilling the SENIEUR protcol. Significantly higher secretion of IL-1-beta, IL-6 and IL-8 after stimulation with LPS were found in the SENIEUR elderly compared to young donors. IL-1-beta, IL-6 and IL-8 were elevated in the whole blood samples of the healthy elderly controls as well. After stimulation of whole blood samples from these healthy elderly with LPS, IL-1 and IL-6 secretion was significantly elevated, but stimulation of their PBMCs showed lower amounts of produced cytokines compared to the PBMCs of healthy young donors. The results suggest that the elvated cytokine releases are caused by an interaction of LPS with a serum factor in the blood of the elderly. Such an overproduction of these inflammatory cytokines by moncytes and neutrophils may be in part responsible for many symptoms elderly people suffer from during an infection with Salmonella.
Insights
Elderly individuals exhibit heightened inflammatory responses to Salmonella lipopolysaccharide (LPS), potentially due to serum factors. This overproduction of cytokines may explain severe infection symptoms in older adults.
Area of Science:
- Immunology
- Gerontology
Background:
- Aging is associated with impaired immune function and increased infection susceptibility.
- Elderly individuals face higher complication rates from infections like Salmonella.
Purpose of the Study:
- To investigate cytokine secretion differences in elderly vs. young individuals upon immune stimulation.
- To explore the role of serum factors in age-related immune responses to bacterial components.
Main Methods:
- Whole blood assays and in vitro peripheral blood mononuclear cell (PBMC) stimulation.
- Stimulation using bacterial lipopolysaccharide (LPS), phytohemagglutinin (PHA), and TSST-1.
- Measurement of interleukin (IL)-1-beta, IL-6, IL-8, and TNF-alpha secretion.
Main Results:
- SENIEUR protocol-adherent elderly showed significantly higher IL-1-beta, IL-6, and IL-8 secretion after LPS stimulation compared to young donors.
- Elevated IL-1-beta, IL-6, and IL-8 were observed in whole blood of healthy elderly controls.
- LPS stimulation of elderly PBMCs yielded lower cytokine production than young PBMCs, suggesting a serum factor interaction.
Conclusions:
- Elevated cytokine release in the elderly upon LPS stimulation appears mediated by a serum factor.
- Monocyte and neutrophil overproduction of inflammatory cytokines may contribute to severe Salmonella infection symptoms in the elderly.
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