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Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation
Published on: May 16, 2016
Endotoxin levels in immunocompromised children with fever
Insights
Unexplained fevers in immunocompromised children may be caused by endotoxemia. This study found elevated endotoxin levels in some children without infection, suggesting endotoxemia as a potential cause of febrile episodes.
Area of Science:
- Pediatrics
- Immunology
- Infectious Diseases
Background:
- Febrile episodes without a clear cause are frequent in immunocompromised children.
- Circulating endotoxin, a pyrogen, is a potential contributor to unexplained fevers.
- A sensitive Limulus amebocyte lysate assay with a chromogenic substrate was developed.
Purpose of the Study:
- To investigate the role of plasma endotoxin in unexplained febrile episodes in immunocompromised children.
- To establish normal plasma endotoxin levels in children.
Main Methods:
- Plasma endotoxin levels were measured using an enhanced Limulus amebocyte lysate assay.
- Assays were performed on 36 immunocompromised children with fever, including convalescent samples.
- Normal endotoxin levels in healthy children were also determined.
Main Results:
- The upper limit of normal plasma endotoxin level in children was determined to be 35 pg (0.10 EU)/ml.
- Five children (14%) exhibited elevated endotoxin levels during febrile episodes without documented infection or bacteremia.
- Endotoxin levels normalized in these children during convalescence.
Conclusions:
- Endotoxemia is a potential cause or contributing factor for unexplained fevers in immunocompromised children.
- The developed assay provides a sensitive and objective method for endotoxin detection.
- Further research is warranted to understand the clinical implications of endotoxemia in this population.
Abstract:
Febrile episodes for which no cause can be found are common in immunocompromised children. We postulated that circulating endotoxin, a known pyrogen, might be responsible for some of these episodes in the absence of documented infection. Plasma endotoxin levels were assayed using a recently developed Limulus amebocyte lysate assay enhanced in sensitivity and objectivity by the addition of a chromogenic substrate. Eighty-seven plasma endotoxin determinations were made in 36 immunocompromised children with fever. Convalescent endotoxin levels and levels in normal children were also obtained. It was concluded that a plasma endotoxin level of 35 pg (0.10 EU)/ml constitutes the upper limit of normal in children. Five children (14%) had elevated endotoxin levels in the course of the febrile episodes, in the absence of bacteremia or clinically diagnosed infection. In each case, the levels returned to normal during convalescence. It is concluded that endotoxemia is a possible cause or contributing cause of unexplained fever in immunocompromised children.
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