Detection of endotoxins and other pyrogens using human whole blood.

S. Fennrich, M. Fischer, T. Hartung, P. Lexa, T. Montag-Lessing, H. G. Sonntag, M. Weigandt, A. Wendel

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


When cells of the immune system, i.e. primarily blood monocytes and macrophages, come into contact with pyrogens (fever-inducing contaminations) they release mediators transmitting the fever reaction through the organism to the thermoregulatory centres of the brain. The new test discussed here exploits this reaction for the detection of pyrogens: human whole blood taken from healthy volunteers is incubated in the presence of the test sample. If there is pyrogen contamination, the endogenous pyrogen interleukin-1 is released, which is then determined by ELISA. According to the pharmacopoeia, the rabbit pyrogen test determines the fever reaction following injection of a test sample. In comparison, the new whole blood assay is more sensitive, less expensive and determines the reaction of the targeted species. Compared to the well established in vitro alternative, i.e. the limulus amebocyte lysate assay (LAL), the new blood assay is not restricted to endotoxins of gram-negative bacteria, it is not affected by endotoxin-binding blood proteins and it reflects the potency of different endotoxin preparations in mammals. Here, interim results of the ongoing optimization and pre-validation are reported and the present state of the evaluation for biological and pharmaceutical drugs are presented.

Original languageEnglish (US)
Pages (from-to)131-139
Number of pages9
JournalDevelopments in biological standardization
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Drug Discovery
  • Public Health, Environmental and Occupational Health


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