Research Articles Mechanisms of Hexachlorobenzene-Induced Adverse Immune Effects in Brown Norway Rats

Figures & data

Figure 1 Representative HE stained lung sections of female BN rats exposed to the control diet (A, ×200) or 450 mg HCB/kg diet (B, C) for 21 days. HCB exposure caused marked perivascular infiltrates of predominantly eosinophinilic granulocytes (B, ×200). Granulomas consisting of monocytes and macrophages and Langerhans-type giant cells were also observed (C, ×40).

TABLE 1 Summary of immunotoxic effects of HCB in the Brown Norway rat^a

Parameter	Dose^b	References
Increased spleen weight	150, 450	Michielsen et al. (1997)
Increased popliteal, axillary, and mandibular LN weight	450	Michielsen et al. (1997, 2002)
Increased number of HEVs in popliteal LN	150, 450	Michielsen et al. (1997)
Granuloma formation in the mesenteric LN	450	Michielsen et al. (1997)
Inflammatory skin lesions: hyperplasia epidermis, activated dermal vessels, infiltrates of neutrophils, macrophages, and eosinophils	150, 450	Michielsen et al. (1997, 1999a)
Inflammatory lung lesions: focal accumulations of macrophages, granuloma formation, perivascular eosinophilic infiltrates, HEV-like venules	150, 450	Michielsen et al. (1997)
Increased total serum IgM and IgE levels	450	Michielsen et al. (1997)
Increased total serum IgG levels	150, 450	Michielsen et al. (1997)
Increased serum IgM levels against ssDNA	150, 450	Michielsen et al. (1997)
Increased in vitro and in vivo airway hyperresponsiveness	450	Michielsen et al. (2001, 2002)
Decreased IL-2 mRNA expression	150	Vandebriel et al. (2000)^c
Increased IL-10 mRNA expression	50	Vandebriel et al. (2000)^c

^aBN rats were exposed to HCB via the diet for 3 or 4 weeks. The table contains only significant changes.

^bDietary HCB concentration in mg/kg diet.

^cIn this study, rats were exposed to HCB for 6 weeks.

TABLE 2 Summary of results of T-cell- and macrophage-dependency of HCB-induced adverse immune effects in the BN rat

Parameter	CsA study^a	Clodronate-liposomes study^b
Skin pathology
Initial development	Delayed	Prevented in 1 out of 6 rats
Severity and lesional area	Decreased	Decreased in 4 out of 6 rats
Lung pathology
Macrophages and granulomas	Not affected	Prevented in 1 out of 6 rats
Eosinophilic infiltration	Prevented	Prevented moderately in 5 out of 6 rats
Humoral responses
Increased levels of IgM against ssDNA	Prevented	Prevented
Increased IgE levels	Prevented	Not investigated
Spleen effects
Splenomegaly	Not affected	Prevented
Increased TNF-α production	Prevented	Prevented
ALN
Enlargement	Prevented	Not affected
Increased TNF-α production	Not investigated	Prevented

^aResults are from experiments performed in HCB-exposed BN rats treated with CsA to decrease the number of peripheral T-cells and inhibit antigen-induced T-cell activation (Ezendam et al., 2004a).

^bResults are from experiments performed in HCB-exposed BN rats treated with clodronate-liposomes to eliminate macrophages (Ezendam, 2004).

Figure 2 Proposed mode of action of HCB-induced adverse immune effects.

Ezendam J., Hassing I., Bleumink R., Vos J. G., Pieters R. Hexachlorobenzene-induced immunopathology in Brown Norway rats is partly mediated by T-cells. Toxicol. Sci. 2004a; 78: 88–95

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Ezendam J. Mechanisms of Hexachlorobenzene-Induced Adverse Immune Effects. Utrecht University, Utrecht 2004

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