Attenuation of the Inflammatory Response in an Animal Colitis Model by Neutrophil Inhibitory Factor, a Novel β<sub>2</sub>-Integrin Antagonist

Meenan, John; Hommes, Daniël W.; Mevissen, M. L. C. M.; Dijkhuizen, S.; Soule, Howard R.; Moyle, Matthew; Büller, Harry R.; Kate, F. W. Ten; Tytgat, G. N. J.; Deventer, S. J. H. Van

doi:10.3109/00365529609010353

Cited by 22 publications

(10 citation statements)

References 24 publications

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“…5-3 . 0 kg) as previously described [10][11][12]. Briefly, animals were anaesthetized by Hypnorm 0 .…”

Section: Induction Of Colitismentioning

confidence: 99%

“…Tissue sections from the area of maximal inflammation were taken into buffered formalin 10% for histopathology and into ice-cold PBS for myeloperoxidase (MPO) content determination. Dialysis fluid samples were processed as previously described [10,11]. Dialysis fluid was extracted through solid-phase extraction columns: Amprep C 2 (Amersham, Aylesbury, UK) for leukotriene B 4 (LTB 4 ) and thromboxane B 2 (TXB 2 ), or Amprep C 18 for prostaglandin E 2 (PGE 2 ).…”

Section: Sample Collection and Processingmentioning

confidence: 99%

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Efficacy of recombinant granulocyte colony-stimulating factor (rhG-CSF) in experimental colitis

Hommes¹,

Meenan²,

Dijkhuizen

et al. 1996

Clinical and Experimental Immunology

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SUMMARYInflammatory bowel disease is associated with mucosal neutrophil recruitment and activatation, mediated in part by arachidonic acid metabolites. G-CSF attenuates the immune response to sepsis and ameliorates glycogen storage disease Ib-related colitis. These actions may be effected through the shedding of neutrophil adhesion molecules, or inhibition of proinflammatory mediator synthesis. Immune complex colitis was used to evaluate the effect of rhG-CSF on colonic mucosal inflammation, neutrophil recruitment and the generation of eicosanoids. Immune complex colitis was induced in White New Zealand rabbits. Animals were pretreated with rhG-CSF either 24 h before induction, or at induction, with dosages of 50 and 200 g/kg. rhG-CSF caused a time-and dose-dependent neutrophilia in all animals. Pretreatment with rhG-CSF resulted in increased tissue myeloperoxidase levels, despite a histologically similar mucosal polymorphonuclear cell infiltrate between treated and control colitis groups. Leukotriene B 4 (LTB 4 ) and thromboxane B 2 (TXB 2 ) dialysis fluid levels were lower in treated animals, in particular in the groups receiving two doses (LTB 4 : both P < 0 : 01; TXB 2 : both P < 0 : 01. Prostaglandin E 2 (PGE 2 ) levels in dialysis fluid of the rhG-CSF-treated animals showed no difference from controls. In this model of experimental colitis, high-dose therapy with G-CSF resulted in a marked decrease of proinflammatory mediators, but mucosal generation of the protective PGE 2 was preserved. These results suggest that prolonged high-dose therapy with G-CSF may have anti-inflammatory effects in colitis.

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“…5-3 . 0 kg) as previously described [10][11][12]. Briefly, animals were anaesthetized by Hypnorm 0 .…”

Section: Induction Of Colitismentioning

confidence: 99%

Section: Sample Collection and Processingmentioning

confidence: 99%

Efficacy of recombinant granulocyte colony-stimulating factor (rhG-CSF) in experimental colitis

Hommes¹,

Meenan²,

Dijkhuizen

et al. 1996

Clinical and Experimental Immunology

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“…α1, β7, β2 and α4β1 Integrins, and P-Selectin Glycoprotein Ligand-1 Antibodies α1 integrin antibodies were found to decrease inflammation in DSS induced colitis in mice which was associated with a decrease in monocyte accumulation in the lamina propria [109]. Similarly, antibodies to β7 and to β2 integrin (neutrophil inhibitory factor) were found to be beneficial in an adoptive transfer model and in formalin model of colitis [110,111].…”

Section: α4β7 Integrin Antibody (Mln-02 or Ldp-02)mentioning

confidence: 98%

Designing and Testing New Therapeutic Modalities for Treatment of Inflammatory Bowel Disease: Role of Experimental Animal Models

Mourad

2005

CMCAIAA

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Experimental models of inflammatory bowel disease (IBD) have provided important information on the pathogenesis of this disease and tremendously helped in designing and testing some new treatment strategies. Every single step during the inflammatory process has been targeted to inhibit or induce a certain specific pathway. Among others, biologic therapy seems to be the most promising future therapy in IBD. Replenishing the microflora by probiotics showed beneficial results in experimental models. Agents that inhibit inflammatory cytokines and effector cells such as antibodies to tumor necrosis factor alpha, interleukin 12 (IL-12), interferon gamma and CD40L lymphocytes, as well as proinflammatory cytokines such as IL-10, IL-11 and transforming growth factor alpha were found to be effective in decreasing the inflammatory reaction in many animal models. Other candidates remain to be tested. A relatively new therapeutic approach is the blockade of effector cell recruitment into the lesions. In this regard, multiple agents were tested in animals and are already in clinical trials including antibodies to α4 integrins, to α4β7 integrins, to mucosal addressin cell adhesion molecule 1, and inhibitors of endothelial intercellular adhesion molecule 1 expression. Another approach aims at the use of growth factors such as growth hormone, trefoil factors and keratinocyte growth factors that have an important role in the healing of the inflamed intestine. Other strategies include transcription factor inhibitors, anti-coagulation and reactive oxygen scavengers. Herbal medicine has also been tried in animals and the possible mode of action has been investigated. Finally, new ways of delivering drugs, antibodies or anti-inflammatory cytokines to the site of inflammation using viral vectors, microsheres or lymphocytes are promising future approaches.

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“…This is especially true in therapies involving specific and potent agents, like anti-inflammatory interleukins (Rogy et al, 2000) and TNF-alpha blockers (Targran et al, 1997), to regulate immunology of these diseases (Kirsner, 1991;Meenan et al, 1996;Sands, 2000). These agents will need more specific targeting of drugs to the diseased sites.…”

Section: Introductionmentioning

confidence: 96%

Accumulation of PEG-liposomes in the Inflamed Colon of Rats: Potential for Therapeutic and Diagnostic Targeting of Inflammatory Bowel Diseases

Awasthi

Goins

Klipper

et al. 2002

Journal of Drug Targeting

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Therapeutic intervention in inflammatory bowel diseases (IBDs) is often associated with severe toxicity related to the nonspecific and ubiquitous interaction of drugs with the organs and tissues. In order to prevent side effects from aggressive and prolonged treatment with glucocorticoids and immunosuppressive agents, preferential accumulation of these potent drugs in diseased tissue is desired. In this work, we report that liposomes show a remarkable tendency to accumulate in inflamed colon of rats with experimental colitis. The disposition of liposomes was monitored by labeling them with Tc-99m followed by gamma camera imaging, and determining biodistribution of radioactivity in various organs. The images showed distinct accumulation of radioactivity in the colon of rats with colitis, while the abdomen of normal rats was conspicuously free of any visible radioactivity. Although images acquired 4 h after Tc-99m-liposome injection were clear enough for diagnostic indication, the real potential of liposomes for drug delivery was evident in 24 h images where the major organs of liposome accumulation were dwarfed by intense colon activity in animals with colitis. On necropsy, 13.5% +/- 5.48 of the activity accumulated in the inflamed colon as compared to only 0.1% in the normal colon, giving a target-to-nontarget ratio of 135. The blood borne radioactivity was 9% +/- 2.12 (colitis) and 25.7% +/- 4.27 (normal), indicating that the decrease in circulating liposomes is associated with an increase in liposome accumulation in the inflammatory site. The other two major organs that accumulated liposomes were spleen (10.7% normal vs. 11% colitis) and liver (8% normal vs. 10.1% colitis). In conclusion, this study demonstrates the innate propensity of liposomes to accumulate in the sites of inflammation and potential of liposomes loaded with therapeutic drugs or diagnostic agents for targeting colitis.

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Attenuation of the Inflammatory Response in an Animal Colitis Model by Neutrophil Inhibitory Factor, a Novel β₂-Integrin Antagonist

Abstract: These results suggest that blockade of CD11b/CD18-mediated mucosal neutrophil recruitment may form part of a strategy for targeted therapeutic intervention in inflammatory bowel disease.

Cited by 22 publications

References 24 publications

Efficacy of recombinant granulocyte colony-stimulating factor (rhG-CSF) in experimental colitis

Efficacy of recombinant granulocyte colony-stimulating factor (rhG-CSF) in experimental colitis

Designing and Testing New Therapeutic Modalities for Treatment of Inflammatory Bowel Disease: Role of Experimental Animal Models

Accumulation of PEG-liposomes in the Inflamed Colon of Rats: Potential for Therapeutic and Diagnostic Targeting of Inflammatory Bowel Diseases

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Attenuation of the Inflammatory Response in an Animal Colitis Model by Neutrophil Inhibitory Factor, a Novel β2-Integrin Antagonist

Abstract: These results suggest that blockade of CD11b/CD18-mediated mucosal neutrophil recruitment may form part of a strategy for targeted therapeutic intervention in inflammatory bowel disease.

Cited by 22 publications

References 24 publications

Efficacy of recombinant granulocyte colony-stimulating factor (rhG-CSF) in experimental colitis

Efficacy of recombinant granulocyte colony-stimulating factor (rhG-CSF) in experimental colitis

Designing and Testing New Therapeutic Modalities for Treatment of Inflammatory Bowel Disease: Role of Experimental Animal Models

Accumulation of PEG-liposomes in the Inflamed Colon of Rats: Potential for Therapeutic and Diagnostic Targeting of Inflammatory Bowel Diseases

Contact Info

Product

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Attenuation of the Inflammatory Response in an Animal Colitis Model by Neutrophil Inhibitory Factor, a Novel β₂-Integrin Antagonist