Green R H
Yale J Biol Med. 1974 Sep;47(3):166-81.
PENICILLIN TOXICITY IN THE GUINEA PIG MAY BE MANIFESTED IN SEVERAL DIFFERENT WAYS, AND IT IS PROPOSED THAT THESE TOXIC EFFECTS BE CATEGORIZED INTO THREE SYNDROMES: (1) toxic syndrome, characterized by acute fatal illness; (2) hemorrhagic syndrome, characterized by delayed illness with leukopenia and thrombocytopenia, and culminating in massive visceral hemorrhages; (3) chronic syndrome, characterized by retardation of growth and alopecia, a condition somewhat resembling "runt disease." A virus having some of the properties of a parvovirus has been isolated repeatedly from animals ill or dying of penicillin-induced disease. This finding has been construed as being activation of a latent virus by this antibiotic, but the relationship, if any, of the phenomenon of viral activation to the syndromes produced by penicillin and its frequent lethal toxicity is unknown. That a strong association exists, however, has been established. Of some 60 guinea pigs which received injections of penicillin three developed tumors and four others were found to have gallstones. A virus similar or identical to the guinea pig virus also has been isolated from hamsters dying of penicillin-induced disease. It is hypothesized that the absorption of endotoxin, resulting from the well known change in intestinal flora caused by penicillin, produces a state of immunodeficiency which regularly gives rise to activation of a latent virus, and perhaps, rarely, to the development of malignant neoplasms.
青霉素对豚鼠的毒性可能以几种不同方式表现出来，有人提出将这些毒性作用分为三种综合征：（1）毒性综合征，其特征为急性致命性疾病；（2）出血性综合征，其特征为伴有白细胞减少和血小板减少的延迟性疾病，并最终导致大量内脏出血；（3）慢性综合征，其特征为生长发育迟缓及脱毛，这种情况有点类似于“发育不良症”。一种具有细小病毒某些特性的病毒已从患青霉素所致疾病或濒死的动物中反复分离出来。这一发现被解释为这种抗生素激活了一种潜伏病毒，但病毒激活现象与青霉素所产生的综合征及其常见的致命毒性之间（如果存在任何关联的话）的关系尚不清楚。然而，已证实它们之间存在着密切关联。在大约60只接受青霉素注射的豚鼠中，有3只发生了肿瘤，另外4只被发现有胆结石。从死于青霉素所致疾病的仓鼠中也分离出了一种与豚鼠病毒相似或相同的病毒。据推测，青霉素引起的肠道菌群众所周知的变化所导致的内毒素吸收会产生一种免疫缺陷状态，这种状态经常会引发潜伏病毒的激活，也许还会很少见地导致恶性肿瘤的发生。
