Production and characterization of monoclonal antibodies against recombinant human tumor necrosis factor/cachectin

Liang, Chunyu; Liang, Shu‐Mei; Jost, Therese; Sand, Astrid; Dougas, Irene; Allet, Bernard

doi:10.1016/0006-291x(86)91157-5

Cited by 25 publications

(7 citation statements)

References 19 publications

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“…Considerable species specificity of TNF has been reported [29] and, therefore, neutralization of rat TNF by anti-(mouse TNF) antiserum in the mouse L929 cell lysis assay may not correspond to its neutralization capacity in a rat Kupffer cell assay. Membrane-bound forms of TNF have been described [30,311.…”

Section: Discussionmentioning

confidence: 99%

Interdependence of tumor necrosis factor, prostaglandin E₂, and protein synthesis in lipopolysaccharide‐exposed rat Kupffer cells

Peters

Karck

Decker

1990

European Journal of Biochemistry

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Kupffer cells are the main producers of tumor necrosis factor‐α (TNF; cachectin) and eicosanoids in the liver exposed to lipopolysaccharide (endotoxin; LPS). A very rapid but transient release of TNF is followed by a slow, steady synthesis of prostaglandin E2 (PGE2). TNF itself is able to provoke eicosanoid synthesis in Kupffer cells; the rate and pattern of prostaglandin production are similar to those observed after treatment with LPS. Anti‐TNF antibodies completely neutralize TNF action on Kupffer cells, thus ruling out any participation of contaminating LPS. LPS stimulation of PGE2 production in Kupffer cells is reduced by the antiserum to 50%, indicating an involvement of TNF in the stimulatory action of LPS. On the other hand, PGE2, a potent inhibitor of LPS‐elicited TNF release, is able to suppress LPS‐ but not TNF‐stimulated eicosanoid synthesis in rat Kupffer cells. In addition to this autocrine circuit, extrahepatic factors participate in the regulation of Kupffer cell activation: glucocorticoids not only inhibit TNF or prostaglandin production, they also reverse the LPS‐specific changes in the prostaglandin pattern of Kupffer cells. LPS, TNF or cycloheximide when given alone in the concentration range applied in this study do not affect the viability of rat Kupffer cells. However, the combinations of cycloheximide and either LPS or TNF cause rapid death of the cultured cells. The cytolytic potential of either combination cannot be alleviated by treatment with glucocorticoids.

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Section: Discussionmentioning

confidence: 99%

Interdependence of tumor necrosis factor, prostaglandin E₂, and protein synthesis in lipopolysaccharide‐exposed rat Kupffer cells

Peters

Karck

Decker

1990

European Journal of Biochemistry

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“…Briefly, samples were titrated in 96-well plates in 0.1 ml medium. To one of the titration series, anti-hTNF monoclonal antibodies (BG 2-4) were added (28). Afterwards, 5 × 10 4 WEHI clone 13 cells were added and after a 24 h incubation period, surviving cells were stained with 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colorimetrically assayed.…”

Section: Blood Samplesmentioning

confidence: 99%

Granulocyte Elastase, Tumor Necrosis Factor-α and Urokinase Levels as Prognostic Markers in Severe Infection

Philippé

Dooijewaard²,

Offner

et al. 1992

Thromb Haemost

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SummaryWe have examined the prognostic value of the levels in the blood of granulocyte elastase-α1-proteinase inhibitor (E-α1-PI) complex, tumor necrosis factor-α (TNF-α) and urokinase-type plasminogen activator (u-PA) in 35 patients with severe infection upon admission to an Intensive Care Unit. Fourteen patients died.No differences for E-α1-PI complex were found between survivors and nonsurvivors, but in all patients the levels on admission were eight-fold higher than the reference value.TNF-α levels, measured by immunoassay, on admission were four times higher in the nonsurvivors than in the survivors (p = 0.0003) and correlated with the severity of the disease (APACHE II score, r = 0.43, p <0.05). TNF-α was not detectable by bioassay.Total u-PA antigen (u-PA Ag), plasmin-activatable single-chain u-PA (scu-PA) and inactive, nonactivatable u-PA (u-PA#) were on admission all two-fold higher in the nonsurvivors (p = 0.0006, 0.003 and 0.0003, respectively), while normal in the survivors. In both, survivors and nonsurvivors, the ratio between scu-PA and u-PA Ag was significantly decreased (p <0.001, compared to a reference group of healthy volunteers), indicative for enhanced conversion of scu-PA to active two-chain u-PA (tcu-PA) and inactive u-PA# during severe infectious disease. tcu-PA was detected in nine of the 35 patients, while virtually undetectable in controls. scu-PA correlated with the Child-Pugh score on admission (r = 0.42, p <0.05). TNF-α correlated with u-PA Ag (r = 0.38, p <0.05) and with u-PA# (r = 0.47, p <0.01).In a stepwise logistic regression analysis, documentation of infection and plasma levels of u-PA Ag contributed most significantly to prediction of patient outcome. Serum levels of TNF-α did not. These results suggest that, in addition to a number of other clinical and laboratory parameters, u-PA Ag can be used as a prognostic marker in patients with severe infection admitted to an Intensive Care Unit.

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“…Anti-rTNF-a Antibody. IgG fraction was prepared by affinity chromatography on protein A-Sepharose (Pharmacia Fine Chemicals, Uppsala, Sweden) from the serum of a rabbit hyperimmunized with purified rTNF-a (12). The antibody activity of this IgG fraction was detected by immunodiffusion in agar against the immunizing antigen, and was quantitated in a TNF assay (13): a solution of 5 mg/ml neutralized the activity of 58 ng rTNF-a up to a dilution of 1 :81,000 .…”

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confidence: 99%

Tumor necrosis factor/cachectin is an effector of skin and gut lesions of the acute phase of graft-vs.-host disease.

Piguet

Grau

Allet

et al. 1987

The Journal of Experimental Medicine

555

242

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Lethally irradiated mice were injected with semiallogeneic, T-depleted bone marrow cells and an amount of peripheral T lymphocytes sufficient to induce graft-vs.-host disease (GVHD) becoming apparent on the second week after the graft and leading to an increasing mortality rate within the following weeks (greater than 90% mortality within 80 d). Mice receiving bone marrow cells alone had no GVHD and were used as controls. Beginning on day 8, mice with GVHD were injected weekly with 2 mg of either rabbit anti-mouse recombinant tumor necrosis factor/cachectin (TNF-alpha) IgG, or normal rabbit IgG. On the 16-18th d, mice were killed to examine the skin and intestinal lesions of the acute phase of GVHD. The anti-TNF treatment resulted in an almost complete prevention of the severe lesions seen in the mice treated with normal rabbit IgG, i.e., the skin epidermal cell necrosis, foci of lichenoid hyperplastic reactions, and loss of the hypodermic fat; in the gut dilatation with marked flattening of the villi and elevation of the crypts, with increased numbers of mitoses and isolated crypt cell necrosis. In addition to preventing these acute lesions, anti-TNF treatment resulted in a significantly decreased mortality (approximately 70% survival at 80 d). These results suggest that during acute GVHD, the activation of grafted lymphocytes leads to a local release of TNF in the cutaneous and intestinal mucosae, which induces epithelial cell alterations and increases the inflammatory reaction.

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Production and characterization of monoclonal antibodies against recombinant human tumor necrosis factor/cachectin

Cited by 25 publications

References 19 publications

Interdependence of tumor necrosis factor, prostaglandin E₂, and protein synthesis in lipopolysaccharide‐exposed rat Kupffer cells

Interdependence of tumor necrosis factor, prostaglandin E₂, and protein synthesis in lipopolysaccharide‐exposed rat Kupffer cells

Granulocyte Elastase, Tumor Necrosis Factor-α and Urokinase Levels as Prognostic Markers in Severe Infection

Tumor necrosis factor/cachectin is an effector of skin and gut lesions of the acute phase of graft-vs.-host disease.

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Production and characterization of monoclonal antibodies against recombinant human tumor necrosis factor/cachectin

Cited by 25 publications

References 19 publications

Interdependence of tumor necrosis factor, prostaglandin E2, and protein synthesis in lipopolysaccharide‐exposed rat Kupffer cells

Interdependence of tumor necrosis factor, prostaglandin E2, and protein synthesis in lipopolysaccharide‐exposed rat Kupffer cells

Granulocyte Elastase, Tumor Necrosis Factor-α and Urokinase Levels as Prognostic Markers in Severe Infection

Tumor necrosis factor/cachectin is an effector of skin and gut lesions of the acute phase of graft-vs.-host disease.

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Interdependence of tumor necrosis factor, prostaglandin E₂, and protein synthesis in lipopolysaccharide‐exposed rat Kupffer cells

Interdependence of tumor necrosis factor, prostaglandin E₂, and protein synthesis in lipopolysaccharide‐exposed rat Kupffer cells