Hexachlorobenzene-induced Immunopathology in Brown Norway rats is partly mediated by T cells.
Hexachlorobenzene (HCB) is a persistent environmental pollutant with (auto)immune effects in humans and rats. The Brown Norway (BN) rat is very susceptible to HCB-induced immunopathology, and oral exposure causes inflammatory skin and lung lesions, splenomegaly, lymph node (LN) enlargement, and increased serum levels of IgE and anti-ssDNA IgM. The role of T cells in HCB-induced immunopathology is unclear and to elucidate this Cyclosporin A (CsA) was used. BN rats were exposed to either a control diet or a diet supplemented with 450 mg/kg HCB for 21 days. CsA treatment started 2 days prior to HCB exposure and rats were injected daily with 20 mg/kg body weight CsA. Treatment with CsA prevented the HCB-induced immunopathology significantly. The onset of skin lesions was delayed and the severity was also strongly decreased. Furthermore, CsA prevented the HCB-induced increase in spleen weight partly and the increase in auricular LN weight completely. The increase in serum IgE and IgM against ssDNA levels was prevented completely. Macrophage infiltrations into the spleen and lung still occurred but infiltrations of eosinophilic granulocytes into the lung were prevented. Restimulation of spleen cells with the T-cell mitogen ConA and the macrophage activator LPS clearly showed that CsA inhibited T-cell activation, but not macrophage activation. Together, our results show that both T cells and macrophages play a prominent role in HCB-induced immunopathology.
Ezendam
Janine
J
Institute for Risk Assessment Sciences (IRAS), Immunotoxicology, Utrecht University, P.O. Box 80.176, 3508 TD Utrecht, The Netherlands. J.Ezendam@iras.uu.nl
Hassing
Ine
I
Bleumink
Rob
R
Vos
Joseph G
JG
Pieters
Raymond
R
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D004277:DNA, Single-Stranded / Q000235:genetics; D004785:Environmental Pollutants / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006581:Hexachlorobenzene / Q000633:toxicity*; D007107:Immune System / Q000187:drug effects*; D007073:Immunoglobulin E / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D008168:Lung / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011914:Rats, Inbred BN; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015430:Weight Gain / Q000187:drug effects
D016207:Cytokines; D004277:DNA, Single-Stranded; D004785:Environmental Pollutants; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007073:Immunoglobulin E; D006581:Hexachlorobenzene; D016572:Cyclosporine