Infliximab induces apoptosis in monocytes from patients with chronic active Crohn's disease by using a caspase-dependent pathway

Lügering, Andreas; Schmidt, Michael; Lügering, Norbert; Pauels, Hans‐Gerd; Domschke, W; Kucharzik, Torsten

doi:10.1053/gast.2001.28702

Cited by 545 publications

(354 citation statements)

References 47 publications

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“…The apoptotic cells showed induction of caspase 3. These changes also correlated with an absolute decrease in the percentage of monocytes in the peripheral blood after INF infusion [20].…”

Section: Effect On Apoptosismentioning

confidence: 60%

“…It is the balance of these proteins that determines the cell's fate. It has been postulated that INF may work to induce apoptosis through these caspase 8-mitochondrial permeability pathways [20].…”

Section: Explanation Of Tnf Signalingmentioning

confidence: 99%

“…Monocytes isolated from the peripheral blood of patients with CD undergo apoptosis after binding of INF in vitro, i.e. a phenomenon associated with increases in caspase 3 activation [20]. Similarly, T lymphocytes maintained in a mixed lymphocyte reaction with monocyte-derived dendritic cells show significant apoptosis in the presence of INF.…”

Section: Limiting Factors Contributing To Disease Restriction In Thermentioning

confidence: 99%

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TNFα blockade in human diseases: Mechanisms and future directions

Wong

Ziring

Korin

et al. 2008

Clinical Immunology

255

162

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Tumor necrosis factor-alpha (TNFα) antagonists have shown remarkable efficacy in a variety of immune-mediated inflammatory diseases (IMIDs). Therapeutic scope and limitations of these agents are reviewed in a recently published article in the Journal. In spite of their therapeutic popularity, little is known about their modes of action in vivo and factors that limit their scope of therapeutic use. Intriguingly, while all TNFα antagonists including blocking antibodies and soluble receptors are effective in certain IMIDs, only anti-TNFα antibodies are effective in other IMIDs. Early efforts at understanding how TNFα antagonists act in IMIDs centered on their ability to neutralize soluble TNFα or to block TNF receptors from binding to their ligands. Subsequent studies suggested a role of complement-mediated lysis or antibody-dependent cell cytotoxicity in their therapeutic effects. More recent models postulate that TNFα blockers may act by affecting intracellular signaling, with the end result being a hastened cell cycle arrest, apoptosis, suppression of cytokine production, or improved Treg cell function. TNFα antagonists can also modulate the functions of myofibroblasts and osteoclasts, which might explain how TNFα antagonists reduce tissue damage in chronic IMIDs. Focusing on the human therapeutic experience, this analytical review will review the biology of mechanisms of action, the limiting factors contributing to disease restriction in therapeutic efficacy, and the mechanism and frequency of treatment-limiting adverse responses of TNFα antagonists. It is hoped that the overview will address the needs of clinicians to decide on optimal use, spur clinical innovation, and incite translational researchers to set priorities for in vivo human investigations.

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“…The apoptotic cells showed induction of caspase 3. These changes also correlated with an absolute decrease in the percentage of monocytes in the peripheral blood after INF infusion [20].…”

Section: Effect On Apoptosismentioning

confidence: 60%

Section: Explanation Of Tnf Signalingmentioning

confidence: 99%

Section: Limiting Factors Contributing To Disease Restriction In Thermentioning

confidence: 99%

See 1 more Smart Citation

TNFα blockade in human diseases: Mechanisms and future directions

Wong

Ziring

Korin

et al. 2008

Clinical Immunology

255

162

View full text Add to dashboard Cite

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“…In a murine model of chronic TB, neutralization of TNF by antibody but not the TNFR fusion molecule exacerbated chronic TB because of better penetration of antibodies into granulomas (19). In humans, higher avidity and better stability of membrane-bound TNF was demonstrated with anti-TNF mAb (20), which in some studies leads to more efficient apoptosis (21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

Risk of tuberculosis is higher with anti–tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: The three‐year prospective french research axed on tolerance of biotherapies registry

Tubach

Salmon

Ravaud

et al. 2009

Arthritis & Rheumatism

576

366

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Objective. Tuberculosis (TB) is associated with anti-tumor necrosis factor (anti-TNF) monoclonal antibody (mAb) therapy, but whether this association is drug-specific remains a concern. Our objective was to describe cases of TB associated with anti-TNF mAb therapy, identify risk factors, and estimate the incidence.Methods. We conducted an incidence study and a case-control analysis to investigate the risk of newly diagnosed TB associated with the use of anti-TNF agents. As part of the French Research Axed on Tolerance of Biotherapies (RATIO) registry, for 3 years we collected cases of TB among French patients receiving anti-TNF mAb therapy for any indication; for each case, 2 patients treated with anti-TNF agents served as control subjects.Results. We collected 69 cases of TB in patients treated for rheumatoid arthritis (n ‫؍‬ 40), spondylarthritides (n ‫؍‬ 18), inflammatory colitis (n ‫؍‬ 9), psoriasis (n ‫؍‬ 1) and Behçet's disease (n ‫؍‬ 1) with infliximab (n ‫؍‬ 36), adalimumab (n ‫؍‬ 28), and etanercept (n ‫؍‬ 5). None of the patients had received correct chemoprophylactic treatment. The sex-and ageadjusted incidence rate of TB was 116.7 per 100,000 patient-years. The standardized incidence ratio (

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“…Because etanercept has potent anti-inflammatory effects in rheumatoid arthritis, 13,14 the mechanisms of the therapeutic efficacy of TNF-binding molecules in Crohn's disease and rheumatoid arthritis seem to differ. Lü gering et al 11 have studied the effects of infliximab, a high-affinity TNF-␣-binding mouse/human chimeric antibody, on circulating monocytes from patients with active Crohn's disease, and showed that a significant fraction of these cells died from apoptosis. This is a surprising finding in view of the fact that TNF-␣ itself can cause apoptosis of target cells through activation of death domain of TNFRI.…”

mentioning

confidence: 99%