Does High Organochlorine (OC) Exposure Impair the Resistance to Infection in Polar Bears (Ursus maritimus)? Part II: Possible Effect of OCs on Mitogen- and Antigen-Induced Lymphocyte Proliferation

Abstract

Previous studies have reported alarmingly high levels of organochlorines (OCs), particularly polychlorinated biphenyls (PCBs), in free-ranging polar bears (Ursus maritimus). In this study plasma concentration of PCBs ranged from 14.8 to 200 ng/g wet weight. The aim of the study was to investigate associations between OCs and lymphocyte proliferation after in vitro stimulation with different mitogens and antigens. In 1998 and 1999, 26 and 30 free-ranging polar bears from Svalbard and Churchill, Canada, respectively, were recaptured 32–40 d following immunization with inactivated tetanus toxoid and hemocyanin from keyhole limpets (KLH) to sensitize lymphocytes. At recapture, blood was sampled for determination of plasma levels of PCBs and organochlorine pesticides (OCPs) and lymphocyte proliferation after in vitro stimulation with specific mitogens—phytohemagglutinin (PHA), pokeweed mitogen (PWM), concanavalin A (Con A), lipopolysaccharide (LPS), and purified protein derivative of Mycobacterium aviumsubsp. paratuberculosis (PPD)—and antigens: tetanus toxoid and KLH. The combinations of ΣPCBs (sum of 12 individual PCB congeners), ΣOCPs (sum of 6 OCPs), and their interactions contributed up to 15% of the variations in the lymphocyte responses. By using multiple regression analyses, followed by classical mathematic function analyses, thresholds for immunomodulation were estimated. Depending on the lymphocyte proliferation response studied, the estimated thresholds for significant immunomodulation were within the concentration ranges 32–89 ng/g wet weight (ww) and 7.8–14 ng/g ww for ΣPCBs and ΣOCPs, respectively. Thus, this study demonstrated that OC exposure significantly influences specific lymphocyte proliferation responses and part of the cell-mediated immunity, which also is associated with impaired ability to produce antibodies (Lie et al., 2004).The authors thank the Norwegian Research Council (NFR, numbers 125693/720 and 140730/720), the Norwegian Ministry of Environment Transport and Effect Program, and the Toxic Substances Research Initiative in Canada for funding this study. The authors thank Tine Borgen for technical assistance in the lymphocyte proliferation test.