THE PASSIVE TRANSFER OF SENSITIVITY TO ANTIGEN-INDUCED FEVER*

Abstract

Immune mechanisms can be involved in a febrile response in humans as evidenced by serum sickness. Similarly, approximately 70% of rabbits immunized with bovine serum albumin (BSA) respond with fevers upon an intravenous challenge with 2 mg pyrogen-free BSA a month after sensitization. To determine whether antigen initiates fever by reacting with circulating antibody, or whether sensitized cells are necessary as in delayed tuberculin hypersensitivity, the following passive transfer studies were conducted. Donor rabbits were immunized with 1-3 subcutaneous injections of 25 mg BSA in incomplete adjuvant. When normal recipients were given 45 ml aliquots of pooled, pyrogen-free antiserum obtained from 16 immunized donors, 11 of 13 responded with fever when challenged later with BSA. Normal recipients given 45 ml of pooled normal rabbit serum remained afebrile after challenge. In contrast, a suspension containing 800 million mono-nuclear cells made from the spleens of immunized rabbits and injected into the abdominal wall of normal recipients failed to passively transfer the capacity to respond with fever. It is concluded that the events resulting in fever following the injection of BSA into sensitized animals are initiated by circulating antibody rather than by sensitized cells, and that fever can be an in vivo secondary manifestation of a primary antigen-antibody reaction.