Further, IgM and specific subclasses of IgG antibodies are involved in the activation of the classical pathway of the match system, which is a critical component of the innate immune response and serves as a first line of defense against contamination (14). Therefore, it is plausible that lower levels of these Igs may be indicative of a reduced immune capacity and greater susceptibility to infection following exposure to TCE, as has been reported in studies of animals exposed to TCE by inhalation. of IgM were reduced by about 38% in workers exposed to TCE compared with unexposed controls (< 0.0001). Serum levels of both IgG and IgM were significantly decreased in workers exposed to TCE levels below 12 p.p.m., the median exposure level. Adjustment for B-cell counts had minimal Olprinone impact on our findings. IgE levels were not significantly different between uncovered and control subjects. These results provide further evidence that TCE is usually immunotoxic at relatively low exposure levels and provide additional biologic plausibility for the reported association of TCE with NHL. Introduction Increasing epidemiological and experimental evidence has suggested that exposure to trichloroethylene (TCE), a common groundwater contaminant and occupational solvent used primarily for metal degreasing, is associated with immunotoxic effects at relatively low exposure levels (1,2). Previously, in a cross-sectional study of occupational TCE exposure, we reported that uncovered workers experienced significant declines in peripheral Olprinone blood Olprinone cell counts, total lymphocytes and some lymphocyte subsets, including Olprinone B cells and CD4+ T cells, as well as in plasma markers of B-cell activation compared with unexposed factory workers (1,2). Moreover, both epidemiological and animal studies have indicated that TCE exposure alters blood levels of cytokines, including the anti-inflammatory IL-4 and type 1 cytokine IFN-, as well as other inflammatory markers (3C5). Collectively, these findings provide evidence that exposure to TCE is associated with immunosuppressive effects and immune dysfunction and provide biological plausibility for the elevated risk of some Olprinone autoimmune and hypersensitivity disorders, as well as non-Hodgkin lymphoma (NHL), that have been observed in some epidemiological studies of TCE exposure (5,6). Immunoglobulins (Igs) are produced by B cells and contribute to the immune response via antigen binding and/or by mediating specific effector functions. Structurally, Igs consist of four polypeptide chains including two light and heavy chains. The type of heavy chain produced determines the Ig isotype, of which five are produced in humans (IgA, IgD, IgG, IgE and IgM), each with its own specific composition and effector functions related to the immune response (7). Both IgG, the most abundant Ig in the body, and IgM, the initial Ig expressed in response to an acute infection, play crucial functions in neutralizing toxins and other immunogens, whereas increased production of IgE specifically is closely associated with hypersensitivity and allergic responses (7). Some evidence from animal studies indicates alterations in serum IgG or IgM levels following exposure to various levels of TCE (8,9). We hypothesized that TCE exposure would impact Ig levels in humans in a manner much like its effect on other immune markers. To our knowledge, no previous epidemiological study has examined serum levels of Igs in healthy workers DPP4 occupationally exposed to TCE. In order to test our hypothesis, we measured serum levels of IgG, IgM and IgE in uncovered workers (= 80) and unexposed controls (= 45) in a cross-sectional study of occupational TCE exposure in Guangdong, China. Materials and methods Study population and exposure assessment The design and exposure assessment protocol of this cross-sectional molecular epidemiology study of factory workers in Guangdong, China, has been explained previously (2). Briefly, subjects were selected from six factories that used TCE in the developing process and from four control factories in the same geographic region, which did not use TCE. Uncovered and unexposed workers were frequency matched on age and sex. Workers with a history of malignancy, chemotherapy, radiotherapy or a previous occupation with notable exposure to benzene, butadiene, styrene and/or ionizing radiation were excluded from the study. Informed consent was obtained from all subjects and the study was approved by the Institutional Review Boards at the U.S. National Cancer Institute and the Guangdong Poison Control Center in China. Full-shift personal air flow exposure measurements using 3M organic vapor monitoring badges were made before the blood sample was collected as explained previously (2). All samples were analyzed for TCE and a subset was analyzed for any panel of other organic hydrocarbons, including benzene, methylene chloride, perchloroethylene and epichlorohydrin. All subjects were interviewed using a questionnaire that assessed demographic and way of life characteristics, as well as occupational history. Analysis of serum IgG, IgM and IgE by enzyme-linked immunosorbent assay All subjects provided blood, buccal, and postshift and overnight urine samples and underwent.