We demonstrated that pretreatment with chromium (Cr) significantly alters inflammatory responses of mice or macrophage cell lines. The mice were pretreated with 50 and 200 mg L(-1) of Cr dissolved in drinking water for 7 or 21 d, respectively. Then, the mice were challenged with lipopolysaccharide (LPS) or saline for 3 h. The body and liver weights significantly decreased after exposure to 200 mg L(-1) of Cr for both 7 and 21 d. Serious infiltration of inflammatory cells around the artery was found in the liver treated with 200 mg L(-1) of Cr for 7 and 21 d. The levels of tumor necrosis factor-α (TNFα) and interleukin-6 (IL6) in peritoneal macrophage significantly increased after the treatment with 200 mg L(-1) of Cr for 7 d. Moreover, LPS-induced increases in the serum levels and the transcriptional status of some cytokine genes were amplified by the Cr pretreatment. In the in vitro test, the RAW264.7 cell line was pretreated with Cr for 3, 6, 12, and 24 h, followed by stimulation with LPS (1 μg mL(-1)) for 6 h. LPS-induced the increases in TNFα, IL6, Interleukin-1α (IL1α), Interleukin-1β (IL1β), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2) mRNA levels were significantly promoted by the pretreatment with Cr for 3, 6, and 12 h, whereas they were weakened by the pre-exposure to Cr for 24 h in a concentration-dependent manner. In addition, LPS-induced the release of TNFα and IL6 in the medium was also significantly enhanced or suppressed by the different Cr pretreatment. The results suggested that Cr had the potential to induce immunotoxicity by altering the inflammatory responses.
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