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Immunomodulatory effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin tested by the popliteal lymph node assay
F Fan1, D M Pinson, K K Rozman
1Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417, USA.
Abstract:
Drugs and other chemicals that have the potential to induce or exacerbate systemic autoimmune diseases in humans are of great concern. The aim of this study was to examine the immune-disregulating potential of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by using the popliteal lymph node (PLN) assay. Chlorpromazine (CPZ) was used as a reference compound for 2 reasons: (a) CPZ is known to elicit a positive response in this assay, and (b) CPZ is a structural analogue of TCDD. Male Sprague-Dawley rats were injected subcutaneously with either TCDD or CPZ into the right hind footpad, whereas vehicle alone was injected into the contralateral footpad. Control rats were injected with vehicle in both hind footpads. Animals were sacrificed on day 7, and their PLNs were removed, weighed, and immersed in 10% formalin. The PLN weight index (the weight ratio of right PLN over left PLN) was significantly higher in both CPZ- and TCDD-treated rats than in controls. Histological examinations of PLNs in the CPZ- and TCDD-treated rats revealed similar morphological changes in both groups (e.g., mild follicular hyperplasia with no evidence of an acute inflammatory response). These results indicate that TCDD has the potential to induce or exacerbate autoimmune-like reactions. Results also suggest that drugs may be useful surrogates to study the mechanism of toxicity of environmental chemicals that cannot be administered to humans.
Insights
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in rats induced autoimmune-like reactions, similar to chlorpromazine (CPZ). This suggests TCDD may exacerbate systemic autoimmune diseases, highlighting the need for further environmental chemical toxicity research.
Area of Science:
- Toxicology
- Immunology
- Environmental Health
Background:
- Systemic autoimmune diseases can be induced or worsened by drugs and chemicals.
- Understanding the immunotoxicity of environmental chemicals like 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is crucial.
Purpose of the Study:
- To investigate the immune-disregulating potential of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
- To assess TCDD's ability to induce or exacerbate autoimmune-like reactions using the popliteal lymph node (PLN) assay.
Main Methods:
- Male Sprague-Dawley rats were used.
- Rats were injected with TCDD or chlorpromazine (CPZ) in one hind footpad and vehicle in the other.
- Popliteal lymph nodes (PLNs) were weighed and examined histologically on day 7.
Main Results:
- Both TCDD and CPZ significantly increased the PLN weight index compared to controls.
- Histological examination showed similar mild follicular hyperplasia in PLNs of both TCDD- and CPZ-treated rats.
- No acute inflammatory response was observed.
Conclusions:
- TCDD has the potential to induce or exacerbate autoimmune-like reactions.
- The popliteal lymph node (PLN) assay is a viable method for assessing TCDD's immunotoxicity.
- Drugs like CPZ can serve as useful models for studying the toxicity mechanisms of environmental chemicals.