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Release of an endogenous pyrogen in vitro from rabbit mononuclear cells
Abstract:
The capacity of rabbit mononuclear cells to release an endogenous pyrogen (EP) in vitro has been studied. After incubation with tuberculin, preparations of predominantly monocytic cells, derived from the respiratory passages of the lungs of rabbits sensitized with BCG, were activated to release EP. Pyrogen production occurred more slowly with lung monocytes than with blood leukocytes of similarly sensitized rabbits and 9 to 10 hr incubation in a fully supportive medium was required to produce clear-cut results. As previously reported with blood leukocytes, mononuclear cells from the lungs of normal animals were also activated by tuberculin but to a lesser degree than were those from specifically sensitized rabbits. Under a variety of conditions, mononuclear cells from either spleen or lymph nodes of the same sensitized rabbits failed to release detectable amounts of pyrogen when incubated with tuberculin in vitro but were activated in a majority of instances when phagocytosis of heat-killed staphylococci was used as the stimulus. Release of pyrogen from lung monocytes appears to be an active process that is both temperature-dependent and requires protein synthesis. Neither serum antibody nor complement appears to play a role in this process. Evidence is presented that the granulocyte is the main source of pyrogen evolved by blood leukocytes incubated in vitro with OT or heat-killed staphylococci, whereas the lung macrophage and/or monocyte is responsible for most of the pyrogen released from the lung cell preparations. From these studies, it is concluded that mononuclear cells can be activated in vitro by several microbial stimuli and must be considered an additional cellular source of EP. The clinical implications of these findings for the pathogenesis of fever in granulomatous diseases where the monocyte is the predominant cell are discussed.
Insights
Rabbit lung mononuclear cells release endogenous pyrogen (EP) after microbial stimulation. Lung monocytes, unlike spleen or lymph node cells, are a significant source of EP, crucial for understanding fever in granulomatous diseases.
Area of Science:
- Immunology
- Cell Biology
- Pathogenesis of Fever
Background:
- Endogenous pyrogen (EP) release by immune cells is a key mechanism in fever development.
- Mononuclear cells, particularly monocytes and macrophages, are implicated in inflammatory responses.
- Previous studies focused on blood leukocytes, leaving the pyrogenic capacity of tissue-resident mononuclear cells less understood.
Purpose of the Study:
- To investigate the capacity of rabbit mononuclear cells from different tissues to release endogenous pyrogen (EP) in vitro.
- To identify the specific cell types responsible for pyrogen production in lung tissue.
- To explore the conditions and stimuli that activate mononuclear cells for EP release.
Main Methods:
- Isolation and incubation of mononuclear cells from rabbit lungs, blood, spleen, and lymph nodes.
- Stimulation of cells with tuberculin (purified protein derivative of tuberculin) and heat-killed staphylococci.
- Measurement of endogenous pyrogen release and assessment of temperature dependency and protein synthesis requirements.
Main Results:
- Mononuclear cells from BCG-sensitized rabbit lungs released EP upon tuberculin stimulation, with slower kinetics than blood leukocytes.
- Lung mononuclear cells from normal rabbits also responded to tuberculin, but to a lesser extent than sensitized cells.
- Spleen and lymph node cells showed minimal EP release with tuberculin but responded to staphylococci; lung macrophages/monocytes were identified as the primary EP source in lung preparations.
Conclusions:
- Mononuclear cells, particularly lung macrophages and monocytes, are a significant source of endogenous pyrogen following microbial stimulation.
- EP release is an active, temperature-dependent process requiring protein synthesis, independent of serum antibody or complement.
- These findings highlight the role of tissue-resident mononuclear cells in fever pathogenesis, especially in granulomatous diseases.