The role of the immune system in hexachlorobenzene-induced toxicity

Hexachlorobenzene (HCB) is a persistent environmental pollutant. The toxici ty of HCB has been extensively studied after an accidental human poisoning in Turkey and more recently it has been shown that HCB has immunotoxic prop erties in laboratory animals and probably also in man. Oral exposure of rat s to HCB showed stimulatory effects on spleen and lymph node weights and hi stology, increased serum IgM levels, and an enhancement of several paramete rs of immune function. Moreover. more recent studies indicate that HCB-indu ced effects in the rat may be related to autoimmunity. In Wistar rats expos ed to HCB, IgM antibodies against several autoantigens were elevated; in th e Lewis rat, HCB differently modulated two experimental models of autoimmun e disease. Oral exposure of rats to HCB induces skin and lung pathology in the rat. Recently several studies have been conducted to investigate whethe r these skin and lung lesions can be related to HCB-induced immunomodulatio n, and these studies will be discussed in this review. HCB-induced skin and lung lesions probably have a different etiology; pronounced strain differe nces and correlation of skin lesions with immune parameters suggest a speci fic involvement of the immune system in HCB-induced skin lesions. The induc tion of lung lesions by HCB was thymus independent. Thymus-dependent T cell s were not likely to be required for the induction of skin lesions, althoug h T cells enhanced the rate of induction and the progression of the skin le sions. No deposition of autoantibodies was observed in nonlesional or lesio nal skin of HCB-treated rats. Therefore, we concluded that it is unlikely t hat the mechanism by which most allergic or autoimmunogenic chemicals work, i.e., by binding to macromolecules of the body and subsequent T- and B-cel l activation, is involved in the HCB-induced immunopathology in the rat. Su ch a thymus-independent immunopathology is remarkable, as HCB strongly modu lates T-cell-mediated immune parameters. This points at a very complex mech anism and possible involvement of multiple factors in the immunopathology o f HCB.