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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Studies on the mechanism of endogenous pyrogen production. III. Human blood monocytes
Abstract:
The characteristics of pyrogen production and release by human blood monocytes were investigated. A dose-response assay of monocyte pyrogen in rabbits indicated a linear relationship of temperature elevation to dose of pyrogen at lower doses. Monocytes did not contain pyrogen when first obtained, nor did they release it spontaneously even after 5 days of incubation in vitro. Pyrogen production was apparent 4 h after stimulation by endotoxin or phagocytosis, and continued for 24 h or more. Puromycin, an inhibitor of protein synthesis, prevented both initiation and continuation of pyrogen production and release. Pyrogen-containing supernates retained most pyrogenic activity during overnight incubation even in the presence of activated cells. Lymphocytes appeared to play no role in either initiation or continuation of pyrogen production in these studies.
Insights
Human monocytes produce pyrogens after stimulation, requiring protein synthesis. These pyrogens, or fever-inducing substances, are released by monocytes and are crucial for immune responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- Pyrogens are fever-inducing substances.
- Monocytes are key immune cells involved in inflammation.
Purpose of the Study:
- To investigate pyrogen production and release by human blood monocytes.
- To understand the kinetics and regulation of monocyte-derived pyrogens.
Main Methods:
- Dose-response assay in rabbits to quantify pyrogen activity.
- In vitro incubation of monocytes with and without stimulants.
- Use of puromycin to inhibit protein synthesis.
Main Results:
- Monocytes do not inherently contain or spontaneously release pyrogens.
- Pyrogen production begins 4 hours after stimulation (endotoxin or phagocytosis) and persists.
- Puromycin inhibits pyrogen production and release, indicating a requirement for protein synthesis.
- Pyrogen activity is stable in supernatant.
- Lymphocytes do not influence pyrogen production.
Conclusions:
- Human monocytes synthesize and release pyrogens following stimulation.
- Protein synthesis is essential for pyrogen production and release.
- Monocyte-derived pyrogens play a significant role in the inflammatory response.
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