Related Experiment Videos
The search for an endogenous activator
Abstract:
Certain febrile diseases are unaccompanied by infection or apparent hypersensitivity. In myocardial infarction or pulmonary embolism, for example, fever has been attributed to inflammation and/or tissue necrosis. Exogenous (microbial) pyrogens stimulate both human and animal monocytes/macrophages to produce endogenous pyrogen (EP) in vitro. To determine if plasma and cellular endogeneous mediators (EMs) of inflammation induced EP production, human mononuclear cells (M/L) were incubated for 18 hours with varying amounts of EM and the supernates assayed for EP in rabbits. Neutrophils (PMNs), which do not generate EP and yet are a feature of acute inflammation, were tested. Neither viable, phorbol myristic acetate-stimulated PMNs nor sonicated PMNs, red blood cells, or M/L stimulated human monocytes to produce EP. Human C3b and C5a, which mediate phagocytosis and chemotaxis, respectively, were also inactive. Despite its chemoattractant properties, the synthetic peptide FMLP failed to induce EP release. Since Poly I:Poly C (PIC: a synthetic, double-stranded RNA) is a potent pyrogen in rabbits, we investigated PIC, as well as a native, single-stranded RNA (from E. coli) and DNA (from calf thymus). None was active in vitro, and only PIC caused fever when given to rabbits intravenously. In summary, we have been unable to find an endogenous activator of EP from human monocytes to explain fevers associated with inflammation alone.
Insights
Researchers investigated endogenous mediators of inflammation to understand fever without infection. They found no endogenous activator in human monocytes that could explain fever solely from inflammation or tissue damage.
Area of Science:
- Immunology
- Inflammation Research
- Fever Pathogenesis
Background:
- Fever can occur without infection or hypersensitivity, often linked to inflammation or tissue necrosis (e.g., myocardial infarction, pulmonary embolism).
- Microbial pyrogens trigger monocytes/macrophages to produce endogenous pyrogen (EP), a key mediator of fever.
Purpose of the Study:
- To determine if plasma and cellular endogenous mediators (EMs) of inflammation stimulate EP production in human monocytes.
- To identify potential endogenous activators of EP release in non-infectious febrile conditions.
Main Methods:
- Human mononuclear cells (M/L) were incubated with various endogenous mediators and tested for EP production in rabbit assays.
- Neutrophils (PMNs), complement factors (C3b, C5a), a synthetic peptide (FMLP), and nucleic acids (Poly I:Poly C, E. coli RNA, calf thymus DNA) were evaluated for EP induction capacity.
Main Results:
- Neither neutrophils, complement factors, nor FMLP stimulated EP release from human monocytes.
- Tested nucleic acids did not induce EP production in vitro; only Poly I:Poly C caused fever in rabbits.
- No endogenous activator was identified in human monocytes to explain fevers associated solely with inflammation.
Conclusions:
- The study failed to identify an endogenous activator from human monocytes that explains fever in the absence of infection.
- Further research is needed to elucidate the mechanisms behind inflammation-induced fever without identifiable infectious triggers.