Chusid M J, Atkins E
J Exp Med. 1972 Aug 1;136(2):227-40. doi: 10.1084/jem.136.2.227.
Rabbits immunized to benzylpenicillin G responded with fever when challenged with a penicillin-serum protein conjugate, but not with penicillin itself. After one or two challenges with conjugate, the rabbits became unresponsive (tolerant) to further injections. This form of hypersensitivity was transferable with plasma of immunized donors to normal rabbits. Blood leukocytes of immunized rabbits incubated with penicillin-protein conjugate and hypersensitive serum released endogenous pyrogen in vitro. Spleen cells from the same animals, on the other hand, were inactive when incubated with this antigen in vitro. These experiments appear to be the first to demonstrate in vitro a possible mechanism of drug-induced fever.
用苄青霉素G免疫的兔子，在受到青霉素 - 血清蛋白结合物攻击时会出现发热反应，但对青霉素本身无此反应。在用结合物进行一两次攻击后，兔子对进一步注射变得无反应（耐受）。这种超敏反应形式可通过免疫供体的血浆转移给正常兔子。用青霉素 - 蛋白结合物和超敏血清孵育免疫兔子的血液白细胞，可在体外释放内源性热原。另一方面，来自相同动物的脾细胞在体外与该抗原孵育时无活性。这些实验似乎是首次在体外证明药物性发热的一种可能机制。
