Interferon gamma, a mediator of lethal lipopolysaccharide-induced Shwartzman-like shock reactions in mice.
Interferon gamma, a mediator of lethal lipopolysaccharide-induced Shwartzman-like shock reactions in mice.
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DOI：
10.1084/jem.171.6.1853
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发表时间：
1990-06-01
期刊：
影响因子：
--
通讯作者：
Billiau A
中科院分区：
文献类型：
--
作者：
Heremans H;Van Damme J;Dillen C;Dijkmans R;Billiau A
通过检测细胞因子或中和抗细胞因子抗体改变综合征病程的能力，研究细胞因子在细菌脂多糖(LPS)引起的全身性Shwartzman样致死性炎症反应发病机制中的作用。在非SPF NMRI小鼠中，连续两次注射粘质链球菌内毒素可引起这种反应：第一次在足垫注射，24小时后静脉注射；准备剂量的大小和途径被发现是关键。用抗干扰素-γ的单抗治疗可以完全阻止这一反应。另一方面，用干扰素-伽马治疗使小鼠对反应的诱发更加敏感。相反，全身注射干扰素-α/β则起到脱敏作用。通过对小鼠血清中细胞因子水平的研究，也证明了内源性细胞因子在这种普遍的Shwartzman反应发病机制中的作用。在给予致命性和非致命性诱导方案的小鼠之间的比较中，发现死亡率与干扰素或肿瘤坏死因子水平的高低有很好的相关性，但与IL-6水平没有相关性。此外，在接受抗干扰素-伽马抗体保护的小鼠中，无法检测到血清中的干扰素和肿瘤坏死因子，而IL-6水平与未受保护的小鼠一样高。这些数据提供的证据表明，在控制内毒素炎症反应的细胞因子中，内源性干扰素-γ占有关键地位。因此，这些发现也为干扰素-γ拮抗剂的临床应用开辟了前景。
The involvement of cytokines in the pathogenesis of a generalized, Shwartzman-like lethal inflammatory response to bacterial lipopolysaccharides (LPS) was studied by testing the ability of cytokines or neutralizing anticytokine antibodies to modify the course of the syndrome. The reaction was elicitable in non-SPF NMRI mice by two consecutive injections of S. marcescens LPS: a first injection in the footpad, followed after 24 h by an intravenous dose; the size and route of the preparatory LPS dose were found to be critical. Treatment with mAbs against IFN-gamma was found to completely prevent the reaction. Treatment with IFN-gamma on the other hand, rendered the mice more sensitive to elicitation of the reaction. In contrast, systemic administration of IFN-alpha/beta exerted a desensitizing effect. The role of endogenous cytokines in the pathogenesis of this generalized Shwartzman reaction was also documented by a study of the cytokine levels in the serum of the mice. In comparisons between mice given lethal and nonlethal induction schedules, a good correlation was found between mortality rates and height of IFN or TNF levels, but no correlation was seen with IL-6 levels. Also, in mice that were protected by anti-IFN-gamma antibody, serum IFN and TNF were undetectable, whereas IL-6 levels were as high as in unprotected mice. These data provide evidence that among the cytokines that govern the inflammatory response to LPS, endogenous IFN-gamma occupies a key position. These findings therefore also open perspectives for clinical application of IFN-gamma antagonists.
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影响因子：
158.5
作者：
MICHIE, HR;MANOGUE, KR;WILMORE, DW
通讯作者：
WILMORE, DW
DOI：
10.1073/pnas.76.11.5939
发表时间：
1979-01-01
影响因子：
11.1
作者：
GALANOS, C;FREUDENBERG, MA;REUTTER, W
通讯作者：
REUTTER, W
DOI：
10.1073/pnas.86.14.5572
发表时间：
1989-07-01
影响因子：
11.1
作者：
GRAU, GE;HEREMANS, H;VASSALLI, P
通讯作者：
VASSALLI, P
DOI：
10.1016/0006-291x(89)92146-3
发表时间：
1989-08-30
影响因子：
3.1
作者：
EVERAERDT, B;BROUCKAERT, P;FIERS, W
通讯作者：
FIERS, W
DOI：
10.1073/pnas.84.12.4273
发表时间：
1987-06-01
影响因子：
11.1
作者：
KETTELHUT, IC;FIERS, W;GOLDBERG, AL
通讯作者：
GOLDBERG, AL