Characterization of the early phase of the tuberculin reaction in rabbits

The dermal response to purified protein derivative (PPD) in rabbits sensitized with Mycobacterium bovis strain Bacille Calmette Guèrin (BCG) is composed of at least two distinct phases. The early phase occurs within 24 h after injection of tuberculin and is characterized by accumulation of polymorphonuclear leukocytes. The second phase is delayed in onset, depending on mononuclear cell accumulation, and constitutes the classic delayed hypersensitivity reaction. The early component of the reaction of PPD is not immunologically specific, in that it can be elicited in either BCG-sensitized or nonsensitized rabbits and appears to be induced by pyrogenic components present in tuberculin preparations. Rabbit fever index assays indicated the presence of sufficient pyrogen in tuberculin PPD to account for the observed reactions; however, Limulus amebocyte pyrogen assays were negative. These findings suggest that tuberculin contains pyrogenic components other than endotoxin. Radiometric assays for mononuclear cell accumulation as well as desensitization experiments indicated that the early phase was independent of the delayed mononuclear phase.