Experimental elimination of tumor necrosis factor in low-dose endotoxin models has variable effects on survival

Franks, A. K.; Kujawa, Krzysztof; Yaffe, Lyn

doi:10.1128/iai.59.8.2609-2614.1991

Cited by 34 publications

(12 citation statements)

References 30 publications

(24 reference statements)

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“…Clearly, galactosamine-sensitized mice develop lethal pathology that is independent of endogenous IFN-␥, either because lethal phenomena other than those in unsensitized mice are triggered or because IFN-␥-triggered pathways are somehow mimicked by galactosamine intoxication. It cannot be questioned that TNF plays a critical role in mediating lethal toxicity in D-galactosamine-sensitized mice: D-galactosamine makes mice exquisitely sensitive to TNF (10); accordingly, D-galactosamine-sensitized mice can be protected against LPS toxicity by anti-TNF antibody (3). Similarly, in the D-galactosamine-SEB syndrome, anti-TNF antibody treatment has been found to exert significant protection (16,17).…”

Section: Discussionmentioning

confidence: 99%

Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release in D-galactosamine-sensitized and unsensitized mice

et al. 1995

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Administration of staphylococcal enterotoxin B (SEB) to BALB/c mice was found to induce a cytokine release syndrome hallmarked by weight loss and hypoglycemia. A neutralizing monoclonal antibody against gamma interferon (IFN-␥) given before SEB counteracted weight loss and prevented hypoglycemia. This protective effect of anti-IFN-␥ antibody was associated with decreased IFN-␥ levels in serum; tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels remained unchanged. A monoclonal anti-IL-6 antibody, known for its ability to cause accumulation of biologically active IL-6 in the circulation, did not modify SEB-induced body weight loss or hypoglycemia. Levels of TNF, IFN-␥, and IL-6 in serum were all more elevated in anti-IL-6-treated mice than in corresponding SEB-challenged control mice. In D-galactosamine-sensitized mice, SEB-induced weight loss but not hypoglycemia was more severe, resulting mostly in death within 24 h. Higher levels of biologically active TNF and IFN-␥ in serum were noted in these mice than in mice receiving SEB only. In D-galactosaminesensitized mice, anti-IFN-␥ antibody did prevent hypoglycemia but failed to reduce the severity of the syndrome. Again, TNF levels in anti-IFN-␥-treated mice remained unchanged. Pretreatment with anti-IL-6 antibody temporarily attenuated SEB-induced hypoglycemia in sensitized mice. Thus, at 6 h post-SEB injection, anti-IL-6-treated mice were less hypoglycemic than corresponding controls. However, at 24 h, hypoglycemia was significantly aggravated. Concomitantly, IL-6 levels were dramatically increased. Neither anti-IFN-␥ nor anti-IL-6 antibody treatment modulated mortality levels in D-galactosamine-sensitized mice. The data obtained with anti-IFN-␥ antibody clearly indicate that endogenous IFN-␥ is instrumental in bringing about hypoglycemia and body weight loss in mice exposed to SEB but also that hypoglycemia is not a crucial determinant of mortality in D-galactosamine-sensitized mice. The data obtained with anti-IL-6 antibody indicate that endogenous IL-6 is involved in regulating the levels of TNF and IFN-␥ in serum.

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Section: Discussionmentioning

confidence: 99%

Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release in D-galactosamine-sensitized and unsensitized mice

et al. 1995

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“…E-mail: takasima@lab.takeda.co.jp. 4 ϫ 10 5 U of this anti-TNF-␣ antibody is sufficient to neutralize up to 100 ng of TNF-␣ per milliliter of blood of lipopolysaccharide-treated mice in vivo (5). The number of survivors was recorded daily.…”

Section: Methodsmentioning

confidence: 99%

Role of tumor necrosis factor alpha in pathogenesis of pneumococcal pneumonia in mice

et al. 1997

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The production and role of tumor necrosis factor alpha (TNF-␣) in pneumococcal pneumonia were investigated in a mouse pneumonia model. When approximately 10 6 CFU of Streptococcus pneumoniae TUM19 were used to inoculate CBA/J mice intranasally, TNF-␣ levels in the lungs and serum began to increase from 1 and 3 days after infection, respectively, concomitantly with the increase in bacterial counts in the lungs. Anti-TNF-␣ antibody accelerated bacterial proliferation in the blood and the death of the mice. Although serum levels of immunoglobulin G antibody against the infecting bacteria were not affected by the anti-TNF-␣ antibody treatment, neutrophil counts in the blood were decreased by the treatment. These results suggest that TNF-␣ produced in the course of pneumococcal pneumonia prevents bacteremia by increasing the number of neutrophils in the blood.

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“…Treatment with anti-TNF-a antibody. According to the method of Frank et al [20], mice were intravenously injected with 4 × 10 5 U of rabbit antimouse TNF-a polyclonal antiserum; sufficient to neutralize circulating TNF-a activity in Con A-treated mice.…”

Section: Assay For Serum Aminotransferase Activities and Cytokine Levmentioning

confidence: 99%

Protection Against Concanavalin A‐Induced Murine Liver Injury by the Organic Germanium Compound, Propagermanium

et al. 1998

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Propagermanium (3-oxygermylpropionic acid polymer) is an organic germanium compound that activates the immune system. In this study, we investigated the action of propagermanium on T-cell-mediated murine hepatic injury induced by concanavalin A (Con A). Oral administration of propagermanium inhibited the development of liver injury about 10 h after ConA injection. Histological analysis demonstrated that propagermanium attenuated the extent of liver damage compared with controls, reducing infiltration by leucocytes, especially CD11b-positive cells. Infiltration by CD4-positive cells was not affected. Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma are crucial for the development of hepatitis in this model. Propagermanium treatment induced significant inhibition of subsequent TNF-alpha production about 10 h after Con A injection, without affecting IFN-gamma, interleukin (IL)-10, IL-4 and IL-12 production. This effect on TNF-production coincided with the inhibition of aminotransferase activity late in the progression of Con A-induced liver injury. These facts suggest that this compound affects the macrophages (Mphi) function in the liver sinusoid. Therefore, Mphi were cultured with liver sinusoidal endothelial cells (SEC) and the effect of propagermanium on TNF-alpha production in the presence of IFN-gamma was determined. TNF-alpha production was reduced significantly in the coculture of Mphi and SEC when Mphi was treated with propagermanium. These results might explain the mechanisms by which propagermanium inhibits Con-A-induced liver injury. That is, propagermanium improves hepatitis through mechanisms including the reduced production of TNF-alpha, without modification of Th1- and Th2-cell function.

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Experimental elimination of tumor necrosis factor in low-dose endotoxin models has variable effects on survival

Cited by 34 publications

References 30 publications

Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release in D-galactosamine-sensitized and unsensitized mice

Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release in D-galactosamine-sensitized and unsensitized mice

Role of tumor necrosis factor alpha in pathogenesis of pneumococcal pneumonia in mice

Protection Against Concanavalin A‐Induced Murine Liver Injury by the Organic Germanium Compound, Propagermanium

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