Monocyte Activation test

The monocyte activation test (MAT) is an in-vitro test based on the human fever reaction with human whole blood or human blood cells (monocytes). It is also used to detect endotoxic and non-endotoxic pyrogens of parenteral products, such as drugs and medical devices. Like the rabbit test, the MAT detects all types of pyrogens. For animal welfare reasons, it is to be used in preference to the rabbit test. The test was included in the European Pharmacopoeia (Ph. Eur. 2.6.30) in 2010.

The activation of monocytes, followed by the polarization of macrophages, is an important step in the normal immune response to pathogens and other relevant stimuli. Depending on the type of activation signal, macrophages can adopt pro- or anti-inflammatory phenotypes characterized by the expression of different patterns of secreted cytokines and surface antigens. This process is disrupted in immunopathologies, resulting in abnormal monocyte activation and/or a bias in macrophage polarization towards one phenotype or the other. Such changes could serve as important diagnostic markers and also as potential targets for the development of immunomodulatory therapy.

The monocyte/macrophage activation assay is a successful example of a cellular assay relevant to atherosclerosis and oncopathology. This assay demonstrated changes in macrophage activation in subclinical atherosclerosis and breast cancer and could also be used to screen a range of natural agents with immunomodulatory activity.

In the test, the test substance is mixed with a human blood sample. The MAT should soon completely replace the so-called "rabbit test". After 16 to 24 hours, the cytokines produced (in particular IL-6, IL-1β and TNF-α) are determined using ELISA. The results are better transferable to humans, as the MAT reacts species-specifically on the basis of human monocytes and does not have to be transferred to another biological system.

The monocyte activation test is an in-vitro alternative to conventional animal tests (e.g. rabbit test) that comply with the guidelines of the regulatory authorities.

1. Ivanova EA et al. (2016) Monocyte Activation in Immunopathology: Cellular Test for Development of Diagnostics and Therapy. J Immunol Res 2016:4789279.