Loppnow H, Libby P, Freudenberg M, Krauss J H, Weckesser J, Mayer H
Tufts University School of Medicine, Boston, Massachusetts.
Infect Immun. 1990 Nov;58(11):3743-50. doi: 10.1128/iai.58.11.3743-3750.1990.
Many pathological effects of gram-negative bacteria are produced by their cell wall-derived lipopolysaccharides (LPSs). Differing pathogenicity of gram-negative LPSs, however, may depend on their capacities to induce cytokines. Thus, we studied the lethal toxicity of four nonenterobacterial LPSs and compared it with their capacity to induce mononuclear cell (MNC)-derived interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF). Unstimulated MNC did not release these cytokines. LPS from the phototrophic strain Rhodobacter capsulatus 37b4 elaborated little toxicity in galactosamine-treated mice (10 micrograms of LPS per mouse was the 100% lethal dose [LD100]) and induced IL-1 and IL-6 release only at high concentrations (10 to 50 micrograms of LPS per ml). R. capsulatus LPS failed to induce TNF activity even at the highest concentration tested (100 micrograms of LPS per ml). In contrast, LPS derived from Pseudomonas diminuta NCTC 8545 or the nodulating species Bradyrhizobium lupini DSM 30140 and Rhizobium meliloti 10406 expressed lethal toxicity (LD100, 1,000, 100, and 10 ng per mouse, respectively) and induced IL-1 or IL-6 (10 to 100, 10, and 1 ng of LPS per ml, respectively) at concentrations 1,000- to 10,000-fold lower than effective levels of R. capsulatus LPS. LPSs from P. diminuta, B. lupini, and R. meliloti also stimulated TNF production and release. MNC accumulated cell-associated IL-1 activities under circumstances in which released activity was readily detected. The cells contained only scant IL-6 activity, indicating release of this mediator rather than intracellular accumulation. Antisera to the respective cytokines inactivated biological activities of the samples selectively. The R. capsulatus LPS inhibited cytokine induction by LPS from P. diminuta, B. lupini, and R. meliloti in coincubation experiments. These results show that the in vivo lethality of the LPSs tested correlates with the induction of monocyte-derived cytokines in vitro. The results of this study suggest that the different lethality of various LPSs from gram-negative bacteria may be due to the differential ability of these LPSs to induce cytokine production.
革兰氏阴性菌的许多病理效应是由其细胞壁衍生的脂多糖（LPS）产生的。然而，革兰氏阴性LPS的致病性差异可能取决于它们诱导细胞因子的能力。因此，我们研究了四种非肠道细菌LPS的致死毒性，并将其与它们诱导单核细胞（MNC）衍生的白细胞介素-1（IL-1）、白细胞介素-6（IL-6）和肿瘤坏死因子（TNF）的能力进行了比较。未受刺激的MNC不释放这些细胞因子。光合菌株荚膜红细菌37b4的LPS在半乳糖胺处理的小鼠中产生的毒性很小（每只小鼠10微克LPS是100%致死剂量[LD100]），并且仅在高浓度（每毫升10至50微克LPS）时诱导IL-1和IL-6释放。即使在测试的最高浓度（每毫升100微克LPS）下，荚膜红细菌LPS也未能诱导TNF活性。相比之下，源自微小假单胞菌NCTC 8545或结瘤物种慢生根瘤菌DSM 30140和苜蓿根瘤菌10406的LPS表现出致死毒性（LD100分别为每只小鼠1000、100和10纳克），并在比荚膜红细菌LPS有效水平低1000至10000倍的浓度下诱导IL-1或IL-6（分别为每毫升10至100、10和1纳克LPS）。来自微小假单胞菌、慢生根瘤菌和苜蓿根瘤菌的LPS也刺激TNF产生和释放。在很容易检测到释放活性的情况下，MNC积累了与细胞相关的IL-1活性。细胞中仅含有少量IL-6活性，表明该介质是释放而不是细胞内积累。针对相应细胞因子的抗血清选择性地灭活了样品的生物活性。在共孵育实验中，荚膜红细菌LPS抑制了来自微小假单胞菌、慢生根瘤菌和苜蓿根瘤菌的LPS诱导的细胞因子。这些结果表明，所测试的LPS的体内致死性与体外单核细胞衍生细胞因子的诱导相关。这项研究的结果表明，革兰氏阴性菌的各种LPS的不同致死性可能是由于这些LPS诱导细胞因子产生的能力不同。
