Immune suppression assays

This new ICH guideline replaces all guidances from EU, USA and Japan. It represents a very pragmatic approach and uses studies, e.g standard toxicity studies, which are conducted anyhow (see Table 15). There is great confidence in the prediction of these assays for any potential of new compounds to induce immune suppression or immune stimulation. This guideline helps to reduce the number of animals and requires additional studies only in special cases for concern. 

Numerous reviews have documented immune modulation in response to metal, pesticide and organic contaminants in fish4,19,37,135. Assays traditionally used to assess perturbations of immune function in fish fall into three broad categories pathogen challenge models, assays that monitor immune suppression/activation or immuno-pathology. Immune suppression/activation is usually measured with assays of phagocytosis, respiratory burst, cell proliferation, as well as quantification of soluble factors such as lysozyme, serum antibody, CRP or complement. 

Anti-Inflammatory Therapeutics. The Streptococcus pneumoniae pulmonary host resistance assay is recommended for anti-inflammatory therapeutics (Komocsar et al., 2007). The Streptococcus pneumoniae pulmonary host resistance model in Lewis rats was used to assess the effects of anti-inflammatory agents on innate immunity. The model was able to predict potential drug suppression of the innate immune response to Streptococcus pneumoniae. The authors stated the ability to rank order the severity of innate immune suppression with multiple test articles in the same study made this model effective in screening potential drug candidates. 

As discussed above, the LTS facilitates investigations of the mechanisms that enable the suppression of DTH by CD8-f Tregs because the assay is complete within 24 h. In other words, to probe the mechanisms and antigen specificity of suppression, manipulations can be made that only influence the suppression of the DTH response after the immunized mice are challenged. 

Chronic exposure to hepatotoxic doses of DMN has also been found to suppress humoral and cellular immunity in mice. DMN is geno-toxic in a wide variety of assays inducing DNA synthesis, chromosomal aberrations, sister chromatid exchange, and bacterial mutations. " The formation of DNA adducts by metabolites of DMN may play a critical role in the carcinogenic process."... 

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