Shalaby M R, Waage A, Aarden L, Espevik T
Institute of Cancer Research, University of Trondheim, Norway.
Clin Immunol Immunopathol. 1989 Dec;53(3):488-98. doi: 10.1016/0090-1229(89)90010-x.
The ability of Escherichia coli-derived lipopolysaccharide (LPS), recombinant (r) interleukin 1-beta (rIL-1 beta), and r murine tumor necrosis factor-alpha (rMuTNF-alpha) to induce interleukin 6 (IL-6) production in vivo was investigated. Peak serum IL-6 concentration was attained after 2 hr of LPS injection into mice. The coinjection of antiserum against rMuTNF-alpha with LPS resulted in a reduction of the induced serum IL-6 level, indicating the involvement of endogenous TNF-alpha in LPS induction of IL-6. Recombinant IL-1 beta and rMuTNF-alpha injected directly caused the production of substantial amounts of IL-6 within 30 min. The injection of a combination of rIL-1 beta and rTNF-alpha induced a significantly greater level of IL-6 than either agent alone. The greater level of serum IL-6 was associated with hypothermia and an increased lethality among mice injected with both cytokines. These data demonstrate the abilities of IL-1 beta and TNF-alpha to induce IL-6 production in vivo and indicate that LPS induction of IL-6 may be mediated, at least partially, through TNF-alpha action. The data describe a new in vivo biologic activity shared between IL-1 beta and TNF-alpha and suggest that IL-6 may be an important effector in the manifestation of TNF-alpha and IL-1 beta actions in vivo.
研究了大肠杆菌衍生的脂多糖（LPS）、重组（r）白细胞介素1-β（rIL-1β）和r小鼠肿瘤坏死因子-α（rMuTNF-α）在体内诱导白细胞介素6（IL-6）产生的能力。向小鼠注射LPS 2小时后达到血清IL-6浓度峰值。将抗rMuTNF-α抗血清与LPS共同注射导致诱导的血清IL-6水平降低，表明内源性TNF-α参与LPS诱导IL-6的过程。直接注射重组IL-1β和rMuTNF-α在30分钟内即可导致大量IL-6的产生。注射rIL-1β和rTNF-α的组合诱导的IL-6水平明显高于单独使用任何一种试剂。更高水平的血清IL-6与体温过低以及注射两种细胞因子的小鼠致死率增加有关。这些数据证明了IL-1β和TNF-α在体内诱导IL-6产生的能力，并表明LPS诱导IL-6可能至少部分通过TNF-α的作用介导。这些数据描述了IL-1β和TNF-α之间共享的一种新的体内生物活性，并表明IL-6可能是TNF-α和IL-1β在体内作用表现中的重要效应因子。
