Immunosuppressive effects and associated compensatory responses in zebrafish after full life-cycle exposure to environmentally relevant concentrations of cadmium

In natural environments, fish survive in polluted water by cadmium (Cd) throughout their whole life cycle. However, little information is available on Cd toxicity considering a life cycle assessment. The present study investigated effects of environmental levels of cadmium (0, 2.5, and 5 μg/L) on immune responses in liver and spleen of zebrafish for 15 weeks, from embryos to sexually maturity. Nitric oxide (NO) levels and iNOS activity declined in liver and spleen of zebrafish exposed to 5 μg/L Cd, suggesting an immunosuppressive effect. The result was further supported by the decreased transcriptional levels of proinflammatory cytokines by Cd, such as interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1β (IL-1β), and tumour necrosis factor-α (TNF-α) in liver. However, a sharp increase in the mRNA levels of these cytokines was observed in spleen of zebrafish exposed to Cd. The increased mRNA expression of these proinflammatory cytokines may be the secondary effect following immunosuppression and just reflect a compensatory mechanism for coping with the decreased immunity, which may explain an increase in mRNA levels and a decrease in iNOS activity in spleen of zebrafish exposed to Cd. In liver, the down-regulated mRNA levels of iNOS paralleled with the decreased iNOS activity, suggesting a synchronous response from a molecular level to a biochemical level. Positive correlations between mRNA expression levels of nuclear transcription factor κB (NF-κB) and proinflammatory cytokines were also observed, suggesting that NF-κB might be required for the protracted induction of inflammatory genes. The corresponding changes in the mRNA levels of the inhibitor of κBα (IκBαa and IκBαb) may form a feedback loop to restore transcriptional activity of NF-κB. Furthermore, splenic ROS levels were increased by 5 μg/L Cd, possibly activating NF-κB pathway. Taken together, immunosuppressive effects and tissue-dependent compensatory responses were demonstrated in zebrafish after full life-cycle exposure to environmental levels of Cd, indicating a compromise between survival and immunity.