Due to their pronounced capability to induce fever, endotoxins and other fever-inducing components are termed pyrogens. The best-characterized endotoxins are lipopolysaccharides which are the main cell wall components of Gram-negative bacteris. Fever may also occur after infection by Gram-negative bacteria, viruses and parasites.

Pyrogen testing should ensure that pharmaceutical products for parenteral use are free of fever-inducing components, as contaminants that causing this condition are a serious threat to patients and, in the worst of cases, may lead to death by septic shock.

Pharmacopoeias describe rabbit pyrogen tests. These tests are based on the fact that pyrogen contaminants in a product administered parenterally lead to an increase in body temperature. However, the monitoring of body temperature is not suitable for the control of all endotoxins. In addition, there is the question of the ethical aspect of animal experimentation.

To overcome these problems, alternatives methods have been proposed to test for pyrogenicity. The Limulus ameobocyte lysate (LAL) test, which is included in pharmacopoeias measures the clotting of the haemolymph of the horseshoe crab in the presence of bacterial endotoxins. This test is specific for endotoxins form Gram-negative bacterial, and does not detect other pyrogenic substances. New methods, using cell lines such as MonoMac-6, THP-1 or RAW264.7 and human whole blood based on the determination of cytokines have been proposed to detect endotoxins.