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IL-4 enhances programmed cell death (apoptosis) in stimulated human monocytes
D F Mangan1, B Robertson, S M Wahl
1Cellular Immunology Section, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
Journal of Immunology (Baltimore, Md. : 1950)
|March 15, 1992
Summary
Interleukin-4 (IL-4) induces programmed cell death (apoptosis) in stimulated human monocytes, reducing their survival. This cytokine-mediated monocyte apoptosis contributes to IL-4's anti-inflammatory effects in chronic conditions.
Area of Science:
- Immunology
- Cell Biology
Background:
- Interleukin-4 (IL-4) is known to reduce pro-inflammatory functions of monocytes/macrophages.
- The impact of IL-4 on monocyte survival remained largely unexplored.
Purpose of the Study:
- To investigate whether IL-4 decreases the survival of human monocytes.
- To determine if IL-4 induces programmed cell death in monocytes.
Main Methods:
- Human monocytes were stimulated with IL-1 or LPS.
- Cell viability was assessed after IL-4 treatment.
- Apoptosis was confirmed by DNA fragmentation analysis.
- Comparative analysis with other cytokines was performed.
Main Results:
- IL-4 caused a concentration-dependent decrease in the viability of stimulated monocytes.
- Nonviable cells exhibited features of apoptosis, including DNA fragmentation.
- IL-4 was uniquely effective in enhancing monocyte cell death compared to other cytokines.
- IFN-gamma antagonized the cell death-promoting effects of IL-4.
- The effect was stimulus-specific, with Con A or CSF-maintained viability unaffected.
Conclusions:
- This study provides the first evidence of cytokine-enhanced programmed cell death in monocytes.
- IL-4 reduces the survival of stimulated monocytes through apoptosis.
- These findings suggest that IL-4's anti-inflammatory effects are partly mediated by decreasing monocyte survival in chronic inflammatory lesions.