Human lymphocyte reactivity after in vitro exposure to technical and analytical grade pentachlorophenol.
To investigate the potential effects of technical pentachlorophenol (PCP-T, contaminated with polychlorinated dioxins and furans) and of analytical grade pentachlorophenol (PCP-A) on the human immune system, in vitro assays with freshly prepared human peripheral blood lymphocytes were used as an alternative to experimental animals. Both cell-mediated and humoral immune functions were examined after direct lymphocyte exposure to PCP-T or PCP-A at concentrations ranging from 0-200 microM. In each case the viability of the treated cells remained within the control value range. T lymphocyte blastogenesis after 3 days incubation with PCP was measured using both optimal and suboptimal mitogen (PHA) concentration. Interleukin-2 activity of 24.5-h supernatants of lymphocytes in response to PHA, pretreated with PCP for 20-24 h, was examined in a bioassay using the mouse IL-2-dependent CTLL-6 cell line. The synthesis of immunoglobulins was determined after stimulation with T-dependent (PWM) and T-independent (KlebsM) polyclonal B cell activators. In the proliferation assay the effects of PCP-T became more evident after suboptimal mitogen stimulation. Whereas after optimal mitogen stimulation blastogenesis was affected only at the highest concentration of 200 microM PCP-T, cell reactivity after suboptimal PHA stimulation was altered by all PCP-T doses. In the lower concentration range PCP-T caused enhanced proliferative responses, but at the two highest PCP-T concentrations cell reactivity was significantly suppressed as compared to the medium controls. Significant differences between the effects of PCP-T and PCP-A could be demonstrated only after optimal mitogen stimulation at the highest PCP concentration (200 microM). In contrast, lymphokine production as well as Ig secretion showed severe dose-dependent suppression after exposure to both PCP-T and PCP-A. The humoral immune response appeared to be more suppressed when cultures were stimulated with T-dependent rather than T-independent mitogens. The two different PCP preparations caused immunosuppression of both lymphocyte functions to the same extent. To summarize, the results of our studies indicate that PCP itself is directly immunotoxic to human immunocompetent cells and the T helper cell subset appears to be especially sensitive to PCP exposure. Furthermore, the observation of a direct effect on humoral immunity is similar to previous results showing considerable alterations of antigen specific antibody production in experimental animals after in vivo exposure.
Lang
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Department of Immunology, University of Kiel, Germany.
Mueller-Ruchholtz
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W
D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D010416:Pentachlorophenol / Q000633:toxicity*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D007376:Interleukin-2; D010416:Pentachlorophenol