Skip to main content
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 2002 Dec;110(12):1169–1173. doi: 10.1289/ehp.021101169

Immunologic effects of dioxin: new results from Seveso and comparison with other studies.

Andrea Baccarelli 1, Paolo Mocarelli 1, Donald G Patterson Jr 1, Matteo Bonzini 1, Angela C Pesatori 1, Neil Caporaso 1, Maria Teresa Landi 1
PMCID: PMC1241102  PMID: 12460794

Abstract

Animal studies indicate that the immune system is one of the most sensitive targets of the toxic effects of 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD). TCDD inhibits immunoglobulin secretion and decreases resistance to bacterial, viral, and parasitic infections in exposed animals. Nearly 20 years after the Seveso, Italy, accident, we measured immunoglobulin and complement plasma levels in a random sample of the population in the most highly exposed zones (n = 62) and in the surrounding noncontaminated area (n = 58). Plasma IgG levels decreased with increasing TCDD plasma concentration (r = -0.35, p = 0.0002). Median IgG concentration decreased from 1,526 mg/dL in the group with the lowest (< 3.5 ppt) TCDD levels to 1,163 mg/dL in the group with the highest (20.1-89.9 ppt) TCDD levels (p = 0.002). The association was significant (p = 0.0004) after adjusting for age, sex, smoking, and consumption of domestic livestock and poultry in multiple regression analysis and persisted after exclusion of subjects with inflammatory diseases and those using antibiotics or nonsteroidal anti-inflammatory drugs. IgM, IgA, C3, and C4 plasma concentrations did not exhibit any consistent association with TCDD levels. We performed a systematic review of all the articles published between 1966 and 2001 on human subjects exposed to TCDD reporting information on circulating levels of immunoglobulins and/or complement components. The literature indicates that the evidence for effects of TCDD on humoral immunity is sparse. Methodologic issues, results, and possible sources of variation between studies are discussed. The possible long-term immunologic effects of TCDD exhibited by the participants of the present study, coupled with the increased incidence of lymphatic tumors in the area of the accident, warrant further investigation.

Full Text

The Full Text of this article is available as a PDF (541.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bertazzi P. A., Consonni D., Bachetti S., Rubagotti M., Baccarelli A., Zocchetti C., Pesatori A. C. Health effects of dioxin exposure: a 20-year mortality study. Am J Epidemiol. 2001 Jun 1;153(11):1031–1044. doi: 10.1093/aje/153.11.1031. [DOI] [PubMed] [Google Scholar]
  2. Birnbaum L. S., Tuomisto J. Non-carcinogenic effects of TCDD in animals. Food Addit Contam. 2000 Apr;17(4):275–288. doi: 10.1080/026520300283351. [DOI] [PubMed] [Google Scholar]
  3. Bäsecke J., Griesinger F., Trümper L., Brittinger G. Leukemia- and lymphoma-associated genetic aberrations in healthy individuals. Ann Hematol. 2002 Jan 30;81(2):64–75. doi: 10.1007/s00277-002-0427-x. [DOI] [PubMed] [Google Scholar]
  4. Colosio C., Corsini E., Barcellini W., Maroni M. Immune parameters in biological monitoring of pesticide exposure: current knowledge and perspectives. Toxicol Lett. 1999 Sep 5;108(2-3):285–295. doi: 10.1016/s0378-4274(99)00100-9. [DOI] [PubMed] [Google Scholar]
  5. Dragan Y. P., Schrenk D. Animal studies addressing the carcinogenicity of TCDD (or related compounds) with an emphasis on tumour promotion. Food Addit Contam. 2000 Apr;17(4):289–302. doi: 10.1080/026520300283360. [DOI] [PubMed] [Google Scholar]
  6. Halperin W., Vogt R., Sweeney M. H., Shopp G., Fingerhut M., Petersen M. Immunological markers among workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Occup Environ Med. 1998 Nov;55(11):742–749. doi: 10.1136/oem.55.11.742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hoffman R. E., Stehr-Green P. A., Webb K. B., Evans R. G., Knutsen A. P., Schramm W. F., Staake J. L., Gibson B. B., Steinberg K. K. Health effects of long-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. JAMA. 1986 Apr 18;255(15):2031–2038. [PubMed] [Google Scholar]
  8. Holsapple M. P., Snyder N. K., Wood S. C., Morris D. L. A review of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced changes in immunocompetence: 1991 update. Toxicology. 1991;69(3):219–255. doi: 10.1016/0300-483x(91)90184-3. [DOI] [PubMed] [Google Scholar]
  9. Jansing P. J., Korff R. Blood levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin and gamma-globulins in a follow-up investigation of employees with chloracne. J Dermatol Sci. 1994 Oct;8(2):91–95. doi: 10.1016/0923-1811(94)90001-9. [DOI] [PubMed] [Google Scholar]
  10. Jennings A. M., Wild G., Ward J. D., Ward A. M. Immunological abnormalities 17 years after accidental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Br J Ind Med. 1988 Oct;45(10):701–704. doi: 10.1136/oem.45.10.701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jung D., Berg P. A., Edler L., Ehrenthal W., Fenner D., Flesch-Janys D., Huber C., Klein R., Koitka C., Lucier G. Immunologic findings in workers formerly exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and its congeners. Environ Health Perspect. 1998 Apr;106 (Suppl 2):689–695. doi: 10.1289/ehp.98106689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kerkvliet N. I. Immunological effects of chlorinated dibenzo-p-dioxins. Environ Health Perspect. 1995 Dec;103 (Suppl 9):47–53. doi: 10.1289/ehp.95103s947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Landi M. T., Consonni D., Patterson D. G., Jr, Needham L. L., Lucier G., Brambilla P., Cazzaniga M. A., Mocarelli P., Pesatori A. C., Bertazzi P. A. 2,3,7,8-Tetrachlorodibenzo-p-dioxin plasma levels in Seveso 20 years after the accident. Environ Health Perspect. 1998 May;106(5):273–277. doi: 10.1289/ehp.98106273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Landi M. T., Needham L. L., Lucier G., Mocarelli P., Bertazzi P. A., Caporaso N. Concentrations of dioxin 20 years after Seveso. Lancet. 1997 Jun 21;349(9068):1811–1811. doi: 10.1016/s0140-6736(97)24025-0. [DOI] [PubMed] [Google Scholar]
  15. Li C. Y., Sung F. C. A review of the healthy worker effect in occupational epidemiology. Occup Med (Lond) 1999 May;49(4):225–229. doi: 10.1093/occmed/49.4.225. [DOI] [PubMed] [Google Scholar]
  16. Løvik M., Johansen H. R., Gaarder P. I., Becher G., Aaberge I. S., Gdynia W., Alexander J. Halogenated organic compounds and the human immune system: preliminary report on a study in hobby fishermen. Arch Toxicol Suppl. 1996;18:15–20. doi: 10.1007/978-3-642-61105-6_2. [DOI] [PubMed] [Google Scholar]
  17. Marth E., Sixl W., Bencko V., Medwed M., Lapajne S., Voncina E., Brumen S. People on the garbage dumps of Cairo: a toxicological in vivo model? Cent Eur J Public Health. 1995 Aug;3(3):154–157. [PubMed] [Google Scholar]
  18. Michalek J. E., Ketchum N. S., Check I. J. Serum dioxin and immunologic response in veterans of Operation Ranch Hand. Am J Epidemiol. 1999 Jun 1;149(11):1038–1046. doi: 10.1093/oxfordjournals.aje.a009749. [DOI] [PubMed] [Google Scholar]
  19. Nagayama J., Tsuji H., Iida T., Hirakawa H., Matsueda T., Ohki M. Effects of contamination level of dioxins and related chemicals on thyroid hormone and immune response systems in patients with "Yusho". Chemosphere. 2001 May-Jun;43(4-7):1005–1010. doi: 10.1016/s0045-6535(00)00462-8. [DOI] [PubMed] [Google Scholar]
  20. Neubert R., Maskow L., Triebig G., Broding H. C., Jacob-Müller U., Helge H., Neubert D. Chlorinated dibenzo-p-dioxins and dibenzofurans and the human immune system: 3. Plasma immunoglobulins and cytokines of workers with quantified moderately-increased body burdens. Life Sci. 2000 Apr 21;66(22):2123–2142. doi: 10.1016/s0024-3205(00)00540-3. [DOI] [PubMed] [Google Scholar]
  21. Nohara Keiko, Fujimaki Hidekazu, Tsukumo Shin ichi, Inouye Kaoru, Sone Hideko, Tohyama Chiharu. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on T cell-derived cytokine production in ovalbumin (OVA)-immunized C57Bl/6 mice. Toxicology. 2002 Mar 5;172(1):49–58. doi: 10.1016/s0300-483x(01)00582-0. [DOI] [PubMed] [Google Scholar]
  22. Ott M. G., Zober A., Germann C. Laboratory results for selected target organs in 138 individuals occupationally exposed to TCDD. Chemosphere. 1994 Nov-Dec;29(9-11):2423–2437. doi: 10.1016/0045-6535(94)90411-1. [DOI] [PubMed] [Google Scholar]
  23. Patterson D. G., Jr, Hampton L., Lapeza C. R., Jr, Belser W. T., Green V., Alexander L., Needham L. L. High-resolution gas chromatographic/high-resolution mass spectrometric analysis of human serum on a whole-weight and lipid basis for 2,3,7,8-tetrachlorodibenzo-p-dioxin. Anal Chem. 1987 Aug 1;59(15):2000–2005. doi: 10.1021/ac00142a023. [DOI] [PubMed] [Google Scholar]
  24. Pocchiari F., Silano V., Zampieri A. Human health effects from accidental release of tetrachlorodibenzo-p-dioxin (TCDD) at Seveso, Italy. Ann N Y Acad Sci. 1979 May 31;320:311–320. doi: 10.1111/j.1749-6632.1979.tb56614.x. [DOI] [PubMed] [Google Scholar]
  25. Sulentic C. E., Holsapple M. P., Kaminski N. E. Putative link between transcriptional regulation of IgM expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin and the aryl hydrocarbon receptor/dioxin-responsive enhancer signaling pathway. J Pharmacol Exp Ther. 2000 Nov;295(2):705–716. [PubMed] [Google Scholar]
  26. Vorderstrasse B. A., Steppan L. B., Silverstone A. E., Kerkvliet N. I. Aryl hydrocarbon receptor-deficient mice generate normal immune responses to model antigens and are resistant to TCDD-induced immune suppression. Toxicol Appl Pharmacol. 2001 Mar 15;171(3):157–164. doi: 10.1006/taap.2000.9122. [DOI] [PubMed] [Google Scholar]
  27. Webb K. B., Evans R. G., Knutsen A. P., Roodman S. T., Roberts D. W., Schramm W. F., Gibson B. B., Andrews J. S., Jr, Needham L. L., Patterson D. G. Medical evaluation of subjects with known body levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin. J Toxicol Environ Health. 1989;28(2):183–193. doi: 10.1080/15287398909531339. [DOI] [PubMed] [Google Scholar]
  28. Zober A., Ott M. G., Messerer P. Morbidity follow up study of BASF employees exposed to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) after a 1953 chemical reactor incident. Occup Environ Med. 1994 Jul;51(7):479–486. doi: 10.1136/oem.51.7.479. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES