Chellman G J, Lukas V S, Eugui E M, Altera K P, Almquist S J, Hilliard J K
Institute of Toxicologic Sciences, Syntex, Inc., Palo Alto, CA 94303.
Lab Anim Sci. 1992 Apr;42(2):146-51.
Three of 14 cynomolgus monkeys given the highest dose of an immunosuppressive drug in a 6-month toxicology study developed B virus (Herpesvirus simiae) oral lesions after 3 months of dosing. This necessitated early removal of all high-dose monkeys from the study due to concerns related to B virus. The incidence and severity of parasitic (Oesphagostomum sp.) lesions of the large intestine were also increased in high-dose animals. Both B virus and Oesophagostomum are enzootic in macaques, and the lesions caused by them were considered secondary to chronic immunosuppression caused by the highest dose of the test compound. Evidence of immunosuppression included decreased lymphocyte counts (B-cells; CD2 and CD8 T-cells), histopathologic evidence of lymphoid suppression, and serum-induced inhibition of lymphocyte mitogen responses. Pathogenesis of the B virus was apparently associated with both activation of latent virus as well as transmission of active virus. Approaches for virologic monitoring of primates and for ensuring optimal safety for primate handlers are discussed.
在一项为期6个月的毒理学研究中，给14只食蟹猴服用了最高剂量的免疫抑制药物，其中3只在给药3个月后出现了B病毒（猴疱疹病毒）口腔损伤。由于与B病毒相关的担忧，这使得必须提前将所有高剂量组的猴子从研究中移除。高剂量组动物大肠的寄生虫（食道口线虫属）损伤的发生率和严重程度也有所增加。B病毒和食道口线虫在猕猴中都是地方性流行的，由它们引起的损伤被认为是由最高剂量的受试化合物导致的慢性免疫抑制的继发结果。免疫抑制的证据包括淋巴细胞计数减少（B细胞；CD2和CD8 T细胞）、淋巴抑制的组织病理学证据以及血清诱导的淋巴细胞有丝分裂原反应抑制。B病毒的发病机制显然与潜伏病毒的激活以及活性病毒的传播有关。文中讨论了对灵长类动物进行病毒学监测以及确保灵长类动物饲养员最佳安全的方法。
