科研之友
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摘要
Oligodeoxynucleotides containing CpG motifs (CpG ODNs) are potent immune activators and are being tested as anti-tumor, antimicrobial agents and as adjuvants in vaccines. Little has been reported, however, about the systematic and comprehensive safety evaluation on repeated CpG ODN administration. To investigate the safety profile of a newly developed CpG ODN, CpG 684, we conducted a 28-day repeated dose toxicity study in rats, at dose levels of 5, 20 and 150 mu g CpG 684 per rat. No abnormalities in clinical observations, growth, urinalysis and bone marrow cell counts were found in CpG 684 treated rats. CpG 684 was proved biologically active, capable of up-regulating the expressions of CD40 and CD86 molecules. The monocyte numbers were increased at the dose levels of 20 and 150 mu g per rat. The spleen weights were increased in female rats at the dose level of 150 mu g per rat. Microscopically, 5, 20 and 150 mu g per rat CpG 684 caused local inflammatory cell infiltration and hyperplasia of fibrous tissue at injection sites; the treatment of 5 and 150 mu g per rat CpG 684 induced enhanced inflammatory reaction in inguinal lymphoid tissue, and the dose of 150 mu g per rat induced cell hyperplasia in white pulp of spleen and white pulp expansion. CpG 684 at 150 mu g per rat led to decreases in peripheral lymphocyte, serum globulin, glucose, alkaline phosphatase and K+ levels in female rats, and induced the decrease in serum albumin and total protein in rats of both sexes. The data from this study will provide an important reference for developing CpG 684 as an adjuvant for vaccines of human use.
