scholarly journals Mouse Model of Oral Infection with Virulent Type A Francisella tularensis

2007 ◽  
Vol 75 (4) ◽  
pp. 1651-1660 ◽  
Author(s):  
R. KuoLee ◽  
X. Zhao ◽  
J. Austin ◽  
G. Harris ◽  
J. W. Conlan ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Francisella Tularensis ◽  
Tumor Necrosis ◽  
Type A ◽  
Oral Infection ◽  
Gamma Interferon ◽  
Health Concern ◽  
High Dose ◽  
Virulent Type ◽  
Necrosis Factor

ABSTRACT Francisella tularensis is a gram-negative facultative intracellular pathogen and the causative agent of tularemia. Little is known about the immunopathogenesis of oral infection with this pathogen. Here, for the first time, we examined the susceptibility of mice to intragastric inoculation with virulent type A F. tularensis and characterized the course of infection and the associated host responses. Both immunocompetent and immunodeficient mice were relatively susceptible to intragastric inoculation of type A F. tularensis with a 50% lethal dose (LD50) of 106 organisms, which was 100,000-fold higher than the LD100 for intradermal or respiratory routes of infection. Mice deficient in gamma interferon or tumor necrosis factor receptors 1 and 2 were more susceptible than wild-type controls to oral infection with a high dose of the pathogen. After oral inoculation, F. tularensis appeared first in the mesenteric lymph nodes (MLN) and then rapidly spread to the livers and spleens, where the organism multiplied to high numbers and induced marked neutrophilic infiltration and severe tissue necrosis. Infected mice showed rapid increases in tissue cytokine mRNA expression, which peaked in the MLN at 2 days postinfection (dpi) and in the liver and spleen at 3 dpi. The levels of gamma interferon, interleukin-1β (IL-1β), IL-6, tumor necrosis factor alpha, macrophage inflammatory protein 1α, KC, interferon-inducible protein 10, and monocyte chemotactic protein 1 were elevated from day 2 postinoculation onward. Moreover, mice intradermally immunized with the live vaccine strain of F. tularensis showed little survival advantage over naive mice after oral challenge with type A F. tularensis. These results suggest that type A F. tularensis is an effective oral pathogen that can cause fatal systemic infection and could pose a public health concern, particularly to immunocompromised individuals, if ingested in contaminated water and food.

scholarly journals Treatment of primary or relapsing limb cancer by isolation perfusion with high-dose alpha-tumor necrosis factor, gamma-interferon, and melphalan

Cancer ◽  
1994 ◽  
Vol 73 (2) ◽  
pp. 483-492 ◽  
Author(s):  
Maurizio Vaglini ◽  
Filiberto Belli ◽  
Mario Ammatuna ◽  
Maria Grazia Inglese ◽  
Renato Manzi ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Gamma Interferon ◽  
High Dose ◽  
Necrosis Factor

Ethanol modulation of tumor necrosis factor and gamma interferon production by murine splenocytes and macrophages

Life Sciences ◽  
1993 ◽  
Vol 52 (15) ◽  
pp. 1319-1326 ◽  
Author(s):  
Guan-jie Chen ◽  
Dennis S. Huang ◽  
Bernhard Watzl ◽  
Ronald R. Watson
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Gamma Interferon ◽  
Interferon Production ◽  
Murine Splenocytes ◽  
Necrosis Factor

scholarly journals Gamma Interferon and Lipopolysaccharide Interact at the Level of Transcription To Induce Tumor Necrosis Factor Alpha Expression

2001 ◽  
Vol 69 (5) ◽  
pp. 2847-2852 ◽  
Author(s):  
Julia Y. Lee ◽  
Kathleen E. Sullivan
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Gamma Interferon ◽  
Necrosis Factor Alpha ◽  
Rnase Protection ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Lipopolysaccharide (LPS) is a very potent inducer of tumor necrosis factor alpha (TNF-α) expression from monocytes and macrophages. Another inflammatory cytokine, gamma interferon (IFN-γ), can potentiate the effects of LPS, but the mechanism is not thoroughly understood. Previous reports emphasized the ability of IFN-γ to upregulate CD14 expression (the receptor for LPS), and nearly all studies have utilized sequential stimulation with IFN-γ followed by LPS to exploit this phenomenon. This study demonstrates that IFN-γ can upregulate the effect of LPS at the level of transcription. Human monoblastic Mono-Mac-6 cells produced up to threefold-greater levels of TNF-α when simultaneously stimulated with LPS and IFN-γ compared to treatment with LPS alone. RNase protection studies showed a similar increase in RNA beginning as early as within 30 min. The synthesis of TNF-α mRNA in IFN-γ- and LPS-treated Mono-Mac-6 cells was also temporally prolonged even though the message turnover rate was identical to that seen in LPS stimulated cells. The modulatory effect of IFN-γ may be mediated by Jak2.

In Vitro Sensitivity of Three Human Renal Tumor Xenografts Towards Tumor Necrosis Factor and Alpha and Gamma Interferon

1989 ◽  
pp. 30-38 ◽  
Author(s):  
A. J. M. C. Beniers ◽  
R. J. A. Van Moorselaar ◽  
W. P. Peelen ◽  
B. T. Hendriks ◽  
U. Otto ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Renal Tumor ◽  
Gamma Interferon ◽  
Tumor Xenografts ◽  
In Vitro Sensitivity ◽  
Necrosis Factor

scholarly journals Gamma-interferon and tumor necrosis factor production after bone marrow transplantation is augmented by exposure to marrow fibroblasts infected with cytomegalovirus

Blood ◽  
1990 ◽  
Vol 76 (5) ◽  
pp. 1046-1053 ◽  
Author(s):  
AS Duncombe ◽  
A Meager ◽  
HG Prentice ◽  
JE Grundy ◽  
HE Heslop ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Tumor Necrosis Factor ◽  
Marrow Transplantation ◽  
Tumor Necrosis ◽  
Gamma Interferon ◽  
Cmv Infection ◽  
Necrosis Factor

Abstract After bone marrow transplantation (BMT), mortality from viral infections such as cytomegalovirus (CMV) remains high. Gamma-Interferon (gamma IFN) and tumor necrosis factor (TNF) are produced constitutively after BMT and have anti-viral properties. To study the effects of these cytokines on CMV interaction with host cells, we have used patient marrow fibroblasts since marrow stroma is a target for CMV infection correlating with myelosuppression in vivo. Both gamma IFN and TNF are constitutively produced by recipient CD3+ and CD16+ lymphocytes, but not by their marrow fibroblasts. Secretion by peripheral blood mononuclear cells is increased if they are cultured with host fibroblasts infected with CMV in vitro and the levels of gamma IFN and TNF produced are within the range that protects fresh fibroblasts from CMV infection. Constitutive secretion of cytokines by lymphocytes declines by 8 weeks after BMT, a time when the risk of CMV disease increases sharply. The in vitro phenomenon that we have described needs to be evaluated in correlative studies on individual BMT recipients to determine whether such a cytokine-mediated defense mechanism against CMV may operate in vivo.

Randomized placebo-controlled clinical trial of high-dose interleukin-2 in combination with a soluble p75 tumor necrosis factor receptor immunoglobulin G chimera in patients with advanced melanoma and renal cell carcinoma.

1997 ◽  
Vol 15 (3) ◽  
pp. 1052-1062 ◽  
Author(s):  
J S Du Bois ◽  
E G Trehu ◽  
J W Mier ◽  
L Shapiro ◽  
M Epstein ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Necrosis Factor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Necrosis ◽  
Interleukin 2 ◽  
Advanced Melanoma ◽  
High Dose ◽  
Biologic Effects ◽  
Necrosis Factor

PURPOSE A randomized, double-blind, placebo-controlled trial was performed to compare the toxicity and biologic effects of treatment with high-dose intravenous (IV) bolus interleukin-2 (IL-2) plus the recombinant human soluble p75 tumor necrosis factor (TNF) receptor immunoglobulin G (IgG) chimera (rhuTNFR:Fc) with high-dose IL-2 alone in patients with advanced melanoma and renal cell carcinoma. PATIENTS AND METHODS Twenty patients with advanced melanoma or renal cell carcinoma were randomized to receive IL-2 (Chiron, Emeryville, CA) 600,000 IU/kg every 8 hours on days 1 to 5 and 15 to 19 (maximum, 28 doses) combined with placebo or the rhuTNFR:Fc fusion protein (Immunex, Seattle, WA) 10 mg/m2 on days 1 and 15 and 5 mg/m2 on days 3, 5, 17, and 19. The impact of rhuTNFR:Fc on IL-2 toxicity and biologic effects was evaluated. RESULTS No clinically significant difference in toxicity was observed in the two treatment arms. The adjusted median number of IL-2 doses administered during cycle 1 was 24.5 (range, seven to 28) and 21.5 (range, five to 27) for the placebo and rhuTNFR:Fc arms, respectively (P = .544). IL-2-induced TNF bioactivity, neutrophil chemotactic defect, and serum IL-6, IL-8, and IL-1 receptor antagonist (IL-1RA) induction were suppressed by rhuTNFR:Fc. Two of nine assessable patients (22%) on IL-2/placebo and three of 10 patients (30%) on IL-2/rhuTNFR:Fc responded. CONCLUSION Despite evidence of in vitro neutralization of TNF functional activity and partial inhibition of other secondary biologic effects of IL-2, rhuTNFR:Fc does not reduce the clinical toxicity associated with high-dose IL-2 therapy. These results suggest that the toxicity and antitumor effects of IL-2 treatment are independent of circulating TNF.

scholarly journals Can very high-dose anti-tumor necrosis factor blockade at onset of rheumatoid arthritis produce long-term remission?

2002 ◽  
Vol 46 (7) ◽  
pp. 1971-1972 ◽  
Author(s):  
Philip G. Conaghan ◽  
Mark A. Quinn ◽  
Philip O'Connor ◽  
Richard J. Wakefield ◽  
Zunaid Karim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
High Dose ◽  
Very High ◽  
Necrosis Factor
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