LACK OF TOLERANCE DEVELOPMENT TO TUMOR-NECROSIS-FACTOR-ALPHA INSIDE THE CENTRAL-NERVOUS-SYSTEM

Tumor necrosis factor alpha (TNF alpha) was repeatedly microinfused in to the lateral ventricle of guinea pig brains at a dose of 200 ng, 4 t imes within 150 min, at intervals of 3 days. In comparison to guinea p igs infused with solvent according to the same time schedule, the anim als responded to TNF alpha with pronounced fevers. The quantity of the fever response was the same after each of the 4 microinfusions of TNF alpha. Three days after the last infusion of TNF alpha or solvent all animals received an intramuscular injection of bacterial lipopolysacc haride (LPS). The fever in response to LPS was the same in both groups . Thus, the reported development of tolerance to repeated systemic adm inistration of TNF alpha(1-3) does not develop inside the blood-brain barrier. Also, the febrile response to LPS is not influenced by repeat ed central pre-treatment with TNF alpha, whereas repeated peripheral t reatment does have an effect(3).