Efficacy and safety of retreatment with anti–tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease

Rutgeerts, Paul; D’Haens, Geert R.; Targan, Stephan R.; Vasiliauskas, Eric A.; Hanauer, S. B.; Present, Daniel H.; Mayer, Lloyd; Hogezand, R. A. van; Braakman, T; DeWoody, Kimberly; Schaible, T.; Deventer, Sander J. van

doi:10.1016/s0016-5085(99)70332-x

Cited by 994 publications

(646 citation statements)

References 18 publications

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“…These effects may clearly be related to the ability of anti-TNF-␣ treatment to protect against TNF-␣-induced apoptosis of IEC. Second, the prolonged remission (several weeks, up to 1 year) obtained with a single infusion of anti-TNF-␣ monoclonal antibody in a subgroup of patients with refractory CD (25,26), which may be due to the proapoptotic effects of anti-TNF-␣ treatment on gut mononuclear cells. Interestingly, our observation of increased apoptosis of IEL after anti-TNF-␣ treatment may suggest a pathogenic role of this T cell population during chronic intestinal inflammation.…”

Section: Discussionmentioning

confidence: 99%

TNF-αneutralization ameliorates the severity of murine Crohn's-like ileitis by abrogation of intestinal epithelial cell apoptosis

Marini

Bamias

Rivera–Nieves

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

183

138

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Tumor necrosis factor ␣ (TNF-␣) is an important mediator of programmed cell death, and TNF-␣ blockade significantly improves disease severity in several inflammatory conditions, including Crohn's disease (CD), one of the idiopathic inflammatory bowel diseases. However, the precise mechanism(s) of action of anti-TNF-␣ therapy in CD remains poorly understood. SAMP1͞YitFc mice develop a spontaneous ileitis with similarities to human CD in regard to histological features as well as response to conventional treatments. In this report, we tested the novel hypothesis that the beneficial effects of anti-TNF-␣ therapy in CD are mediated by a mechanism that involves down-regulation of intestinal epithelial cell (IEC) apoptosis. Similar to the efficacy of monoclonal anti-TNF-␣ antibodies in human CD, a single injection of a chimeric anti-murine TNF-␣ antibody into SAMP1͞YitFc mice resulted in a marked suppression of intestinal inflammation and epithelial cell damage compared with mice injected with an isotype control antibody. These effects were associated with a significant reduction in apoptosis of freshly isolated IEC as assessed by propidium iodide staining and DNA laddering. In contrast, an increase in lamina propria mononuclear cell apoptosis was observed in anti-TNF-␣-treated mice compared with control. These results were confirmed in vivo by using the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling-assay. In addition, neutralization of TNF-␣ reduced membrane bound FAS͞CD95 expression in IEC from SAMP1͞YitFc mice compared with control antibody. These data demonstrate a novel mechanism of action of anti-TNF-␣ therapy that involves homeostatic regulation of mucosal cell apoptosis, which results in the net decrease of chronic inflammation typically found in CD.

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Section: Discussionmentioning

confidence: 99%

TNF-αneutralization ameliorates the severity of murine Crohn's-like ileitis by abrogation of intestinal epithelial cell apoptosis

Marini

Bamias

Rivera–Nieves

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

183

138

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“…Recently, TNF␣ blockade has also opened new perspectives for the treatment of SpA: significant clinical and laboratory improvements in patients with active SpA treated with infliximab have been reported (12)(13)(14)(15)(16). Also, in patients with treatment-resistant Crohn's disease (CD), infliximab has shown to be effective in reducing the symptoms (17,18) and healing the enterocutaneous fistulas (19).…”

mentioning

confidence: 99%

Antinuclear antibodies following infliximab treatment in patients with rheumatoid arthritis or spondylarthropathy

Rycke¹,

Kruithof²,

Damme³

et al. 2003

Arthritis & Rheumatism

191

106

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Objective. To investigate the effect of infliximab treatment on antinuclear antibodies (ANAs), antidouble-stranded DNA (anti-dsDNA), antinucleosome, antihistone, and anti-extractable nuclear antigen (anti-ENA) antibodies in rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients.Methods. Sera from 62 RA and 35 SpA patients treated with infliximab were tested at baseline and week 30 (RA group) or week 34 (SpA group). ANAs were tested by indirect immunofluorescence (IIF) on HEp-2 cells. Anti-dsDNA antibodies were detected by IIF on Crithidia luciliae and by enzyme-linked immunosorbent assay (ELISA) and were further isotyped with ␥, , and ␣ chain-specific conjugates at various time points. Antinucleosome antibodies were tested by ELISA. Antihistone and anti-ENA antibodies were detected by line immunoassay.Results. Initially, 32 of 62 RA patients and 6 of 35 SpA patients tested positive for ANAs. After infliximab treatment, these numbers shifted to 51 of 62 (P < 0.001) and 31 of 35 (P < 0.001), respectively. At baseline, none of the RA or SpA patients had anti-dsDNA antibodies. After infliximab treatment, 7 RA patients (P ‫؍‬ 0.016) and 6 SpA patients (P ‫؍‬ 0.031) became positive for anti-dsDNA antibodies. All 7 anti-dsDNA-positive RA patients had IgM and IgA anti-dsDNA antibodies.

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“…Using flow cytometric detection of intracellular leukocyte cytokine production, we have shown that steroids inhibit Th1 and inflammatory cytokine production while upregulating IL-10 synthesis (4). The importance of inflammatory cytokines is evident from the successful and safe therapeutic use of antibodies against TNF-␣ in bringing Crohn's disease into remission (5,6). The nonspecific anti-inflammatory treatment being used in the conventional management of patients with IBD (apart from those mentioned) has not changed much since the 1970s and new therapeutic agents are keenly sought.…”

mentioning

confidence: 99%

Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: Potential therapeutic use in the treatment of inflammatory bowel disease

2002

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BackgroundCytokines involved in inflammatory bowel disease (IBD) direct a predominantly cell‐mediated T‐ helper‐1 (Th1) immune response. The nonspecific anti‐inflammatory treatment being used in the management of patients with IBD has not changed much since the 1970s and new therapeutic agents are keenly sought. Several compounds isolated from Allium sativum (garlic) modulate leukocyte cell proliferation and cytokine production.MethodsTo investigate the possible therapeutic effects of garlic in the treatment of patients with IBD, whole blood and peripheral blood mononuclear cells (PBMCs) were stimulated in the presence of various concentrations of garlic extract and the effect on leukocyte cytokine production was determined in vitro using multiparameter flow cytometry.ResultsMonocyte interleukin (IL)‐12 production was inhibited significantly in the presence of low concentrations of garlic extract (≥0.1 μg/ml total protein). Monocyte IL‐10 production increased significantly and monocyte tumor necrosis factor‐alpha (TNF‐α), IL‐1α, IL‐6, IL‐8, T‐cell interferon‐gamma (IFN‐γ), IL‐2, and TNF‐α decreased significantly in the presence of ≥10 μg/ml garlic extract. Twenty to fifty percent of the immunomodulatory activity of garlic extract on cytokine production was acid labile. The inhibitory activity of methylprednisolone, a commonly used anti‐inflammatory in IBD, with garlic on leukocyte cytokine production was additive.ConclusionsBy inhibiting Th1 and inflammatory cytokines while upregulating IL‐10 production, treatment with garlic extract may help to resolve inflammation associated with IBD. An in vivo animal model study needs to be undertaken to determine the significance of these in vitro findings. Cytometry 48:209–215, 2002. © 2002 Wiley‐Liss, Inc.

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Efficacy and safety of retreatment with anti–tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease

Cited by 994 publications

References 18 publications

TNF-αneutralization ameliorates the severity of murine Crohn's-like ileitis by abrogation of intestinal epithelial cell apoptosis

TNF-αneutralization ameliorates the severity of murine Crohn's-like ileitis by abrogation of intestinal epithelial cell apoptosis

Antinuclear antibodies following infliximab treatment in patients with rheumatoid arthritis or spondylarthropathy

Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: Potential therapeutic use in the treatment of inflammatory bowel disease

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