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Neutralization of pyrogen‐induced tumour necrosis factor by its type 1 soluble receptor in guinea‐pigs: effects on fever and interleukin‐6 release
Author(s) -
Roth Joachim,
Martin Dave,
Störr Birgit,
Zeisberger Eugen
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.267bo.x
Subject(s) - muramyl dipeptide , tumor necrosis factor alpha , lipopolysaccharide , receptor , endocrinology , chemistry , medicine , guinea pig , cytokine , necrosis , pharmacology , immunology , immune system
1 A soluble form of the tumour necrosis factor (TNF) type 1 receptor (referred to as TNF binding protein, TNF‐bp) at a dose of 1 mg per animal, or an equivalent volume of solvent, was injected together with 10 μg kg −1 lipopolysaccharide (LPS) or 50 μg kg −1 muramyl‐dipeptide (MDP) directly into the arterial circulation of guinea‐pigs and the effects on circulating TNF or interleukin‐6 (IL‐6) and on abdominal temperature were studied. 2 At 15 or 60 min after injection, LPS‐induced and MDP‐induced circulating TNF was below the detection limit of the assay and thus completely neutralized in animals treated with TNF‐bp. In the control group, TNF was still below the limit of detection in most animals 15 min after LPS was injected; in some animals small traces of TNF could already be detected at that time. However, 60 min after administration of LPS, large amounts of TNF (19508 ± 4682 pg ml −1 ) were measured in the control group. MDP‐induced TNF in plasma was below the limit of detection 15 min after MDP was injected, and rose to 10862 ± 3029 pg ml −1 60 min after injection. 3 Low levels of circulating IL‐6 (20‐40 international units (IU) ml −1 ) were measured in all groups of animals 15 min after injection of LPS or MDP. This value corresponds to the baseline activity of IL‐6 in plasma of guinea‐pigs. One hour after administration of LPS, IL‐6 rose to 5442 ± 1662 IU ml −1 in the control group and to a significantly lower value of 1485 ± 179 IU ml −1 in guinea‐pigs treated with TNF‐bp. One hour after injection of MDP, circulating IL‐6 was 2614 ± 506 IU ml −1 in the control group, while the corresponding value in animals treated with TNF‐bp again was significantly lower (873 ± 312 IU ml −1 ). 4 The second phase of the characteristic biphasic LPS fever in guinea‐pigs was significantly attenuated in animals treated with TNF‐bp. The shorter first phase of the febrile response to LPS was identical in both groups of animals. 5 The late phase of MDP‐induced fever (7‐22 h after injection) was depressed by treatment with TNF‐bp, while the first phase of MDP‐induced fever (0‐7 h after injection) was significantly enhanced by the neutralization of TNF by TNF‐bp.