TY - JOUR
T1 - Development validation and applications of the monocyte activation test for pyrogens based on human whole blood
AU - Schindler, Stefanie
AU - Von Aulock, Sonja
AU - Daneshian, Mardas
AU - Hartung, Thomas
PY - 2009
Y1 - 2009
N2 - Microorganisms such as Gram-negative or Gram-positive bacteria, viruses and fungi contain components that activate the innate immune system. These components, called pyrogens (Greek: pyros=fire), can occur independently of viable microorganisms and are a major safety concern in parenterally administered drugs, since they can cause severe reactions such as fever, organ failure, and shock in the recipient. So far these drugs have been tested by injecting them intravenously into rabbits and measuring their fever reaction or, alternatively, by the Limulus Amoebocyte Lysate (LAL) test, employing the coagulation of the hemolymph lysate of Limulus polyphemus. Both tests have inherent limitations. A new in vitro monocyte activation test (MAT) based on human whole blood, capable of measuring all pyrogens relevant to the human patient, introduced in this journal in 1995, was validated and recently accepted by European Pharmacopoeia and US FDA. This review describes its principle, development, validation and the wide spectrum of applications, such as for testing of medical devices, blood products, toxic or immunomodulatory drugs, dialysis liquids, lipidic parenterals, and air quality. This alternative method promises to replace the rabbit pyrogen test fully and to overcome several limitations of the LAL assay.
AB - Microorganisms such as Gram-negative or Gram-positive bacteria, viruses and fungi contain components that activate the innate immune system. These components, called pyrogens (Greek: pyros=fire), can occur independently of viable microorganisms and are a major safety concern in parenterally administered drugs, since they can cause severe reactions such as fever, organ failure, and shock in the recipient. So far these drugs have been tested by injecting them intravenously into rabbits and measuring their fever reaction or, alternatively, by the Limulus Amoebocyte Lysate (LAL) test, employing the coagulation of the hemolymph lysate of Limulus polyphemus. Both tests have inherent limitations. A new in vitro monocyte activation test (MAT) based on human whole blood, capable of measuring all pyrogens relevant to the human patient, introduced in this journal in 1995, was validated and recently accepted by European Pharmacopoeia and US FDA. This review describes its principle, development, validation and the wide spectrum of applications, such as for testing of medical devices, blood products, toxic or immunomodulatory drugs, dialysis liquids, lipidic parenterals, and air quality. This alternative method promises to replace the rabbit pyrogen test fully and to overcome several limitations of the LAL assay.
KW - Alternatives to animals
KW - Interleukin-1β
KW - Monocyte activation test
KW - Validation study
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M3 - Review article
C2 - 20383472
AN - SCOPUS:79952198005
SN - 0946-7785
VL - 26
SP - 265
EP - 277
JO - ALTEX
JF - ALTEX
IS - 4
ER -