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Hexachlorobenzene (HCB) is a persistent environmental pollutant that causes adverse immune effects in man and rat. 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. T cells play an important role but do not account for all adverse effects induced by HCB. Macrophages are probably also important and the relationship between macrophages and T cells was further investigated. To eliminate macrophages clodronate-liposomes were used. Furthermore, a kinetic study was performed to obtain insight in the early phase of the HCB-induced immune response. Also, experiments were performed to detect specific memory T cells. Therefore, an adoptive transfer study was performed. Our results indicate that macrophages are indeed involved in HCB-induced skin lesions, lung eosinophilia, and elevation of IgM against ssDNA. Kinetics showed that both skin and lung lesions appeared early after exposure. Moreover, immune effects could not be adaptively transferred. Thus, both macrophages and T cells are involved in HCB-induced immune effects but HCB exposure does not lead to specific T cell sensitization. Presumably, HCB exposure induces macrophage activation, thereby generating adjuvant signals that polyclonally stimulate T cells. Together, these events may lead to the observed immunopathology in BN rats.

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. [ABSTRACT FROM AUTHOR]