Differential effect of isotype on efficacy of anti-tumor necrosis factor alpha chimeric antibodies in experimental septic shock.

Suitters, Amanda; Foulkes, Roly; Opal, Steven M.; Palardy, John E.; Emtage, J.S.; Rolfe, Mark W.; Stephens, Sue; Morgan, A; Holt, Alex; Chaplin, L

doi:10.1084/jem.179.3.849

Cited by 65 publications

(27 citation statements)

References 37 publications

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“…One possible explanation is that the early elevation in plasma TNF caused the activation of other systems, which were responsible for the subsequent haemodynamic changes (Billiau & Vandekerckhove, 1991 (Suitters et al, 1994). Other groups have examined the effectiveness of TNF antibodies in several different models of endotoxaemia, and most reports agree that TNF antibodies are capable of reducing mortality rates in endotoxaemia (Beutler et al, 1985a;Tracey et al, 1987a;Mathison et al, 1988;Hinshaw et al, 1990;Suitters et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…The single doses were therefore chosen on the basis of our previous work (Gardiner et al, 1991b;1992b;Waller et al, 1994). The doses of antibodies used in the present study were chosen on the basis of previous work (Suitters et al, 1994) Bradykinin (Bachem, U.K.), was dissolved in saline containing 1% bovine serum albumin, and salbutamol hemisulphate salt (Sigma) was dissolved in saline containing ascorbic acid (1 mmol 1-1). The hamster murine chimeric anti-TNF monoclonal antibodies (TN3gl and TN3g2a, Suitters et al, 1994) (Celltech Therapeutics) were obtained in sterile antibody solution (TN3gl:-50 mM sodium acetate, 100 mM NaCl; TN3g2a:-50 mM sodium acetate) at pH 5.5.…”

Section: Regional Haemodynamicsmentioning

confidence: 99%

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Lack of effect of TNF antibodies on the cardiovascular sequelae of lipopolysaccharide infusion in conscious rats

Waller

Gardiner

Jose³

et al. 1995

British J Pharmacology

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1 The aims of the present study were to determine the profile of tumour necrosis factor (TNF) release, and the effect of monoclonal antibodies to TNF, on the changes in regional haemodynamics and the responses to vasodilator and vasoconstrictor challenges, during a continuous 24 h low dose infusion of lipopolysaccharide (LPS) in conscious rats. 2 Male Long Evans rats were chronically instrumented for measurement of regional haemodynamics (renal, superior mesenteric and hindquarters) and were challenged with 3 min infusions of acetylcholine (22 nmol min-'), methoxamine (120 nmol min-'), salbutamol (0.83 nmol min-') and bradykinin (14.4 nmol min-'). The rats were given either saline, or the TNF antibodies, TN3gl or TN3g2a, 1 h before the start of a continuous infusion of LPS (150 pg kg -' h -') and were subsequently re-tested with the vasodilator and vasoconstrictor challenges 2, 6 and 24 h after the start of the LPS infusion. 3 Prior to infusion of LPS, TNF was not detectable in the plasma. During continuous infusion of LPS there was a transient elevation in plasma TNF levels, reaching a maximum (-2300 pg ml-') after approximately 1 h, and returning to undetectable levels after approximately 3 h of LPS infusion. 4 In the saline pretreated group, after 1-2 h of LPS infusion, there was a small hypotension and a marked renal vasodilatation; 6 h after the start of LPS infusion there was a minor elevation in MAP above control levels, renal vasodilatation was maintained and a hindquarters vasoconstriction occurred; after 24 h of LPS infusion, there was a hypotension and renal and hindquarters vasodilatation. There were significant reductions in the tachycardic and renal vasodilator responses and an enhanced depressor response to acetylcholine after 24 h of LPS infusion. LPS infusion also caused a generalized hyporesponsiveness to the cardiovascular effects of methoxamine and salbutamol. The major changes in response to bradykinin were reduced tachycardic and enhanced depressor responses throughout the LPS infusion, a biphasic decrease and increase in renal conductance and enhanced hindquarters vasodilatation at 24 h. 5 Pretreatment with either TN3gl or TN3g2a antibodies had no major effects on the changes in resting haemodynamics, or on the changes in response to methoxamine, salbutamol or bradykinin challenges during LPS infusion. However, the tachycardic responses to acetylcholine were generally preserved, and its hypotensive effect after 24 h of LPS infusion was not enhanced after TN3gl or TN3g2a pretreatment. Thus, despite substantial, but transient, elevation of plasma TNF levels during continuous LPS infusion, it appears that the majority of cardiovascular changes were dependent on factors other than plasma TNF.

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Section: Discussionmentioning

confidence: 99%

Section: Regional Haemodynamicsmentioning

confidence: 99%

Lack of effect of TNF antibodies on the cardiovascular sequelae of lipopolysaccharide infusion in conscious rats

Waller

Gardiner

Jose³

et al. 1995

British J Pharmacology

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“…It binds both free and membranebound TNF, and causes apoptosis of TNF-producing cells [622]. Immune processes initiated by complement fixation and antibody-mediated cellular cytotoxicity are also possibly mediated by interaction with infliximab and TNF [623]. Infliximab is delivered intravenously; IBD patients typically receive an initial loading dose regimen of three infusions at weeks 0, 2, and 6, and subsequently receive maintenance infusions every 8 weeks (Fig.…”

Section: Infliximabmentioning

confidence: 99%

Inflammatory Bowel Disease

Stenson

Hanauer

Cohen

2008

Textbook of Gastroenterology

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In the US, H. pylori vacA shows allelic variation in the signal sequence (which may be type sla, slb or s2) and the mid-region (type ml or m2). Previous PCR-based vacA mid-region typing classified most, but not all, Asian and South American strains tested as ml or m2. We now sought to investigate vacA mid-region diversity further.MotlmodL We studied 13 Japanese, 6 Chinese, 9 Thai, and 8 Peruvian H. pylori isolates. cagA was identified by colony hybridisation (CH), vacA signal sequence was typed by PCR, and vacA mid-region was typed proximally by CH and distally by PCR. Sections of the vacA mid-region from 8 strains were PCR-amplified, sequenced, and compared with known sequences from 8 other strains.Rcuts Of the 36 Asian and South American strains studied, 35 were cagA+ (the cagA-was Peruvian) and 35 were vacA sla (1 cagA + Peruvian was slb). vacA mid-regions from the 13 Japanese strains were not PCR-amplified by ml or m2-specific primers, but hybridised weakly with an ml probe. Sequence analysis of vacA from 1 Japanese strain revealed 91% nucleotide identity with the ml probe but only 71% identity with the m2 probe. The previously equivocal Thai and Peruvian strains also had ml-like mid-region sequences. A Chinese strain was ml in the proximal mid-region and m2 distally, showing a clear crossover site. Final mid-region types were: Japanese, all 13 ml; Chinese, 1 ml, 1 ml/m2, 4 m2; Thai, 3 ml, 6 m2; Peruvian 4 ml, 4 m2. Distal mid-region sequences of 16 strains, compared over 294 bp, clustered into 2 groups, ml and m2. Nucleotide identity between ml and m2 strains ranged from 73-78%. Within groups, m2 strains were less diverse than ml strains (m2 range 94-99.7%, ml 88-99.3%, p<0.001). Sequence analysis of 7 ml and 3 m2 strains over 1.1kb proximally showed maintenance of clustering outside the 294bp region C duions These Asian and South American strains are similar in terms of cagA status and vacA sla genotype, but fall into 2 vacA midregion groups. ml sequences are more diverse than m2, and thus may be phylogenetically older. The vacA sequence of 1 Chinese strain suggests recombination in vivo between ml and m2 alleles. Introduction: H.pylori antimicrobial susceptibility is an important determinant ofthe efficacy of eradication therapies'. The prevalence of antimicrobial resistance varies within the UK and may increase given the increased use of eradication therapy. This multicentre study assesses the prevalence and possible associations ofH.pylon antimicrobial resistance. Methods: H.pylon was isolated from antral biopsies of patients undergoing routine endoscopy and cultured according to standard microbiological methods. Antimicrobial resistance was determined using "E-tests" or disc tests (tinidazole only) with breakpoints defined by previous studies. Results: H.pyloni was isolated from 32% (1222/3823) of patients and antimicrobial susceptibility determined in 90% (1077/1222) Previous case-control studies of IBD have used hospital or community derived controls. There are obvious inherent biases in both metho...

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“…mAb 120.G8 (17) was obtained from Schering-Plough. Blocking hamster anti-murine TNF-␣ (TN3-19.12g1) (26,27) was provided by Celltech. mAbs to rat Ags, Ig (OX12), TCR-␣ (R73), CD6 (OX52), CD8 (OX8), CD45RA (OX33), CD103 (OX62), and CD172a (OX41), were purified from cell culture supernatants and used unconjugated or conjugated to FITC or biotin.…”

Section: Reagents and Mabsmentioning

confidence: 99%

Regulation of Intestinal Dendritic Cell Migration and Activation by Plasmacytoid Dendritic Cells, TNF-α and Type 1 IFNs after Feeding a TLR7/8 Ligand

Yrlid

Milling

Miller

et al. 2006

The Journal of Immunology

100

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Dendritic cells (DCs) migrating via lymph are the primary influence regulating naive T cell differentiation, be it active immunity or tolerance. How DCs achieve this regulation in vivo is poorly understood. Intestinal DCs are in direct contact with harmless or pathogenic luminal contents, but may also be influenced by signals from epithelial cells, macrophages, or other resident or immigrant cells. To understand the role of TLR7 and TLR8 in regulating intestinal DC function, we fed a TLR7/8 ligand (resiquimod (R-848)) to rats and mice and examined DC in pseudoafferent lymph (rat) and mesenteric lymph nodes (MLNs). Oral R-848 induced a 20- to 30-fold increase in DC output from the intestine within 10 h due to a virtually total release of lamina propria DCs. This resulted in an accumulation of DCs in the MLNs that in mice was completely TNF-α dependent. Surprisingly, intestinal lymph DCs (iL-DCs) released by R-848 did not up-regulate CD86, but did up-regulate CD25. In contrast, MLN-DCs from R-848-stimulated rats and mice expressed high levels of CD86. This DC activation in MLNs was dependent on type 1 IFNs. The major source of these rapidly released cytokines is plasmacytoid DCs (pDCs) and not classical DCs, because depletion of pDCs significantly reduces the R-848-stimulated increase in serum cytokine levels as well as the accumulation and activation of DCs in MLNs. These experiments show that TLR-mediated regulation of iL-DC functions in vivo is complex and does not depend only on direct iL-DC stimulation, but can be regulated by pDCs.

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Differential effect of isotype on efficacy of anti-tumor necrosis factor alpha chimeric antibodies in experimental septic shock.

Cited by 65 publications

References 37 publications

Lack of effect of TNF antibodies on the cardiovascular sequelae of lipopolysaccharide infusion in conscious rats

Lack of effect of TNF antibodies on the cardiovascular sequelae of lipopolysaccharide infusion in conscious rats

Inflammatory Bowel Disease

Regulation of Intestinal Dendritic Cell Migration and Activation by Plasmacytoid Dendritic Cells, TNF-α and Type 1 IFNs after Feeding a TLR7/8 Ligand

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