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Screening tests for autoimmune-related immunotoxicity.
1Research Institute of Toxicology (RITOX)-Immunotoxicology, Utrecht University, The Netherlands. r.pieters@ritox.vet.uu.nl
Environmental Health Perspectives
|September 30, 1999
Summary
The popliteal lymph node assay (PLNA) shows promise for screening chemical-induced autoimmune risks. Various PLNA types can identify immunostimulating chemicals, aiding in predicting adverse autoimmune effects.
Area of Science:
- Immunotoxicology
- Environmental Health
- Drug Safety
Background:
- Many chemicals can trigger or worsen autoimmune diseases in humans.
- Standard toxicity tests often fail to detect these complex adverse effects.
- Validated predictive animal models for chemical-induced autoimmunity are lacking.
Purpose of the Study:
- To review the popliteal lymph node assay (PLNA) for screening systemic immunosensitizing and autoimmunogenic potential.
- To discuss various PLNA types and their relevance to chemically induced immunostimulation.
- To assess the utility of PLNA in predicting chemical-induced autoimmune effects.
Main Methods:
- Description of primary PLNA: measuring popliteal lymph node enlargement post-injection.
- Explanation of secondary and modified PLNAs for assessing T-cell involvement and anamnestic responses.
- Review of over 100 compounds tested, including drugs and environmental pollutants.
Main Results:
- Primary PLNA distinguishes immunostimulating from innocent chemicals.
- Secondary and modified PLNAs assess T-cell mediated responses and sensitization.
- Results show good correlation with known autoimmunogenic and allergic potentials.
- No false negatives were observed when chemical metabolism was considered.
Conclusions:
- PLNA is a promising tool for (pre)screening autoimmunogenic potential of chemicals.
- Secondary and modified PLNAs are valuable for mechanistic insights.
- Further validation is needed before widespread adoption as a standard test for autoimmunogenicity.