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Volker Daniel,¹ Wolfgang Huber,² Klausdieter Bauer,³ Caner Suesal,¹ Christian Conradt,⁴ and Gerhard Opelz¹

¹Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany; ²Private Practice, Heidelberg-Wieblingen, Germany; ³Labor PD Dr. K. Bauer, Saarbrücken, Germany; ⁴Institute of Medical Biometry, University of Heidelberg, Heidelberg, Germany

Abstract

Pentachlorophenol (PCP) , hexachlorocyclohexane-, -ß, and - (HCH-, -ß, and -) , polychlorinated biphenyls (PCBs) , and hexachlorobenzene (HCB) are widely distributed industrial chemicals. They are suspected to induce immunologic impairments in exposed individuals. We examined dose-response relationships of blood levels of these chemicals with cellular (numbers of lymphocyte subpopulations, in vitro lymphocyte response) or humoral (plasma cytokine levels, immunoglobulin autoantibodies) immunologic dysfunctions. We studied 146 patients who had been occupationally exposed primarily to PCBs for more than 6 months. Lymphocyte subpopulations, in vitro responses to mitogens and allogeneic stimulator cells, plasma neopterin, cytokines, soluble cytokine receptors, soluble adhesion molecules, anti-Ig autoantibodies, and liver transaminases were determined. Blood levels of the different compounds were strongly correlated with one another. There were only weak dose-response relationships between blood levels of PCBs with cellular immune parameters, and of HCHs and HCB with humoral immune parameters. An exception was the statistically significant negative association of HCB with interferon- (IFN-) , indicating that HCB has a significant impact on Th1 lymphocytes. Patients with HCB blood levels above the mean of 1,109 ng/L more often had undetectable IFN- blood levels than patients below the mean. Patients with increased PCB 138 (> 710 ng/L) had more frequently undetectable interleukin-4 blood levels than patients with PCB 138 below the mean, and patients with increased PCB 101 (> 31 ng/L) more often had low DR+ cell counts in the blood (< 190/µL) than patients with PCB 101 below the mean. To assess possible cumulative effects, we compared patients who had blood levels of all compounds below background with patients who had blood levels of all compounds above background. Patients with low or absent blood levels of the compounds studied had higher IFN- plasma levels, providing some evidence for a cumulative effect of several weakly active compounds. In conclusion, exposure to PCBs, HCB, or HCHs is associated with weak immunologic abnormalities. These results contrast with those obtained in earlier studies of blood levels of PCP, which showed a strong dose-dependent relationship with immunologic impairments. Our data suggest that long-term exposure of patients to HCB suppresses IFN- production. Key words: cytokines, hexachlorobenzene, hexachlorocyclohexane, immune function, lymphocytes, polychlorinated biphenyls. Environ Health Perspect 109:173-178 (2001) . [Online 25 January 2001]

http://ehpnet1.niehs.nih.gov/docs/2001/109p173-178daniel/ abstract.html

Address correspondence to V. Daniel, Institute of Immunology, University of Heidelberg, Im Neuenheimer Feld 305, D-60120 Heidelberg, Germany. Telephone: +49 6221 56 4018. Fax: +49 6221 56 4200. E-mail: Volker_Daniel@med.uni-heidelberg.de

We acknowledge the skillful technical assistance of G. Schmeckenbecher, N. Cetinkaya, M. Kutsche-Bauer, C. Hoffmann, R. Seemuth, and N. Schwind.

Received 31 March 2000 ; accepted 28 September 2000.