Authors
Baccarelli, A., Mocarelli, P., Patterson, D.G., Bonzini, M., Pesatori, A., Caporaso, N., Landi, M.T.

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

Journal
Environmental Health Perspectives, 110 (12): 1169-1173. 2002

Summary
In 1976 an industrial accident contaminated the residential area surrounding Seveso, Italy with the dioxin, tetra-chlorinated dioxin (TCDD). Shortly thereafter, three zones were established based on soil TCDD levels. The zones were designated A, B, and R in order of decreasing contamination. Once in the body, dioxins tend to accumulate in adipose tissue, where it can be stored for many years. TCDD is the most toxic member of the dioxin family of chemical contaminants and it has a long biological half-life (> 7 years). In animal studies, TCDD has been shown to produce immunotoxicity. Briefly, the immune system functions through humoral and cell-mediated immunity. Humoral immunity involves protein compounds called 'antibodies' or 'immunoglobulins. There are 5 classes of immunoglobulins (IgG, IgM, IgA, IgD, IgE) that are released by specialized white blood cells (B-lymphocytes) in response to a foreign antigen.

The present study was designed to determine if there was a difference in immune parameters between subjects living in exposed residential areas surrounding Seveso and those living in unexposed areas approximately 20 years after the accident.

The authors randomly sampled 62 subjects from the most contaminated zones (A and B) and 59 subjects from the surrounding non-contaminated areas (non A, B and R zones). Subjects were matched by gender, decade of age, and cigarette smoking status. An in-depth personal interview was conducted to gather information about each subject's medical history and medication use in the week before study. TCDD serum levels were obtained using high resolution mass spectrometric analysis and plasma immunoglobulins, IgA, IgG, and IgM and complement components C3 and C4 were also measured. Several other factors that may have been associated with either TCDD levels or immune status were considered in the analysis including: age, sex, smoking status, body mass index, consumption of domestic livestock and poultry, alcohol consumption, acute and chronic medical conditions and current medication use.

The results showed a significant negative correlation between IgG levels and increasing TCDD levels in the exposed subjects (r=-0.35, p=0.0002), indicating that IgG antibody levels were lower in subjects with high TCDD levels. This association was slightly more pronounced in males than females and the association remained significant after adjusting for other factors that have been found in the past to be associated with lower IgG levels such as age, sex, smoking, and consumption of domestic livestock (p=0.0004). When exposed verses unexposed subjects were compared, subjects in the contaminated areas had significantly lower IgG levels. Other immune parameters investigated by the authors were not found to have any association with TCDD exposure.

The negative correlation between IgG and TCDD levels is an interesting finding. IgG antibodies provide protective capacity against microbial challenge. Children and adults with B-cell related deficiencies are more susceptible to certain viral and bacterial infections. Although there was a significant negative correlation with increasing TCDD levels, only one subject had IgG levels below the normal range (<878 mg/dl). However, the clinical implications of this study are uncertain. Having lowered antibody levels does not necessarily translate into health effects. Other limitations to this study include the relatively small sample size and the time lag between accidental exposure and the exposure measurements (20 years). Regardless, this study is considered important because the Seveso accident has been well characterized and the residents of the area have been followed by health care professionals for many years following the accident making this a unique population for the study of the health effects associated with TCDD exposure.