Lack of endotoxin tolerance with respect to TNF alpha production in the subarachnoid space.
To study endotoxin tolerance in the subarachnoid space 0.1 mg of endotoxin derived from Neisseria meningitidis was injected intracisternally into rabbits on 2 consecutive days. On day 1 the maximum peak level of TNF alpha was 7 ng/ml 2 h after injection, whereas on day 2 the highest levels were 3.6 ng/ml and 3.7 ng/ml, respectively, 1 and 2 h after injection. Pretreatment with intravenous endotoxin 5 or 21 h before consecutive intracisternal endotoxin did not affect the cerebrospinal fluid (CSF) levels of TNF alpha. In contrast, there was a marked endotoxin tolerance with respect to TNF alpha in the systemic circulation. Cells appearing in the CSF 5, 12 and 20 h after intracisternal injection of endotoxin were harvested, cultured, and then stimulated with 0.1 mg/ml of endotoxin. In 10 experiments a marked TNF alpha production in the range 10-70 ng/ml was detected in the supernatants, whereas unstimulated cells did not produce TNF alpha. We conclude that tolerance to endotoxin does not develop in the subarachnoid space as evaluated by the present experimental design. The pattern of TNF alpha production and endotoxin tolerance is distinctly different in the subarachnoid space and systemic circulation.
Steinshamn
S
S
Department of Medicine, University Hospital of Trondheim, Norway.
Waage
A
A
D000818:Animals; D002478:Cells, Cultured; D004361:Drug Tolerance; D004731:Endotoxins / Q000009:adverse effects*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D011817:Rabbits; D013346:Subarachnoid Space / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000134:cerebrospinal fluid
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha