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Evidence that anti-tumor necrosis factor therapy with both etanercept and infliximab induces apoptosis in macrophages, but not lymphocytes, in rheumatoid arthritis joints: extended report.
Arthritis Rheum. 2005 Jan; 52(1):61-72.AR

Abstract

OBJECTIVE

Treatment of rheumatoid arthritis (RA) with tumor necrosis factor (TNF) antagonists is highly effective, but their mechanisms of action are not completely clear. Since anti-TNF therapy induces a decrease in synovial cellularity, this study focused on the modulation of RA synovial apoptosis following treatment with either soluble TNF receptor (etanercept) or TNF chimeric monoclonal antibody (infliximab).

METHODS

Apoptosis (TUNEL and active caspase 3 staining) and cell surface markers were evaluated by immunohistochemistry in synovial biopsy samples obtained before and after 8 weeks of treatment with etanercept (12 patients) or infliximab (9 patients). We also determined by flow cytometry the in vitro effect of etanercept and infliximab on apoptosis of RA mononuclear cells derived from the synovial fluid (SF) and peripheral blood (PB).

RESULTS

Eight weeks of treatment with etanercept and with infliximab significantly increased synovial apoptosis. This change was accompanied by a significant decrease in the synovial monocyte/macrophage population. The decrease in lymphocyte numbers did not reach statistical significance. In vitro, 24 hours of incubation with either etanercept or infliximab induced apoptosis of the SF monocyte/macrophage population. PB monocyte/macrophages were less susceptible to anti-TNF-mediated apoptosis. No changes in the rate of apoptosis were observed in the lymphocyte population derived from either SF or PB.

CONCLUSION

In RA patients, both etanercept and infliximab are able to induce cell type-specific apoptosis in the monocyte/macrophage population. This suggests a potential pathway that would account for the diminished synovial inflammation and the decreased numbers of synovial macrophages evident after TNF blockade.

Authors+Show Affiliations

Rheumatology Research Laboratory, CMM L8:04, Karolinska University Hospital, S-171 76 Stockholm, Sweden. Anca.Catrina@cmm.ki.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Controlled Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15641091

Citation

Catrina, Anca Irinel, et al. "Evidence That Anti-tumor Necrosis Factor Therapy With Both Etanercept and Infliximab Induces Apoptosis in Macrophages, but Not Lymphocytes, in Rheumatoid Arthritis Joints: Extended Report." Arthritis and Rheumatism, vol. 52, no. 1, 2005, pp. 61-72.
Catrina AI, Trollmo C, af Klint E, et al. Evidence that anti-tumor necrosis factor therapy with both etanercept and infliximab induces apoptosis in macrophages, but not lymphocytes, in rheumatoid arthritis joints: extended report. Arthritis Rheum. 2005;52(1):61-72.
Catrina, A. I., Trollmo, C., af Klint, E., Engstrom, M., Lampa, J., Hermansson, Y., Klareskog, L., & Ulfgren, A. K. (2005). Evidence that anti-tumor necrosis factor therapy with both etanercept and infliximab induces apoptosis in macrophages, but not lymphocytes, in rheumatoid arthritis joints: extended report. Arthritis and Rheumatism, 52(1), 61-72.
Catrina AI, et al. Evidence That Anti-tumor Necrosis Factor Therapy With Both Etanercept and Infliximab Induces Apoptosis in Macrophages, but Not Lymphocytes, in Rheumatoid Arthritis Joints: Extended Report. Arthritis Rheum. 2005;52(1):61-72. PubMed PMID: 15641091.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence that anti-tumor necrosis factor therapy with both etanercept and infliximab induces apoptosis in macrophages, but not lymphocytes, in rheumatoid arthritis joints: extended report. AU - Catrina,Anca Irinel, AU - Trollmo,Christina, AU - af Klint,Erik, AU - Engstrom,Marianne, AU - Lampa,Jon, AU - Hermansson,Ylva, AU - Klareskog,Lars, AU - Ulfgren,Ann Kristin, PY - 2005/1/11/pubmed PY - 2005/2/16/medline PY - 2005/1/11/entrez SP - 61 EP - 72 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 52 IS - 1 N2 - OBJECTIVE: Treatment of rheumatoid arthritis (RA) with tumor necrosis factor (TNF) antagonists is highly effective, but their mechanisms of action are not completely clear. Since anti-TNF therapy induces a decrease in synovial cellularity, this study focused on the modulation of RA synovial apoptosis following treatment with either soluble TNF receptor (etanercept) or TNF chimeric monoclonal antibody (infliximab). METHODS: Apoptosis (TUNEL and active caspase 3 staining) and cell surface markers were evaluated by immunohistochemistry in synovial biopsy samples obtained before and after 8 weeks of treatment with etanercept (12 patients) or infliximab (9 patients). We also determined by flow cytometry the in vitro effect of etanercept and infliximab on apoptosis of RA mononuclear cells derived from the synovial fluid (SF) and peripheral blood (PB). RESULTS: Eight weeks of treatment with etanercept and with infliximab significantly increased synovial apoptosis. This change was accompanied by a significant decrease in the synovial monocyte/macrophage population. The decrease in lymphocyte numbers did not reach statistical significance. In vitro, 24 hours of incubation with either etanercept or infliximab induced apoptosis of the SF monocyte/macrophage population. PB monocyte/macrophages were less susceptible to anti-TNF-mediated apoptosis. No changes in the rate of apoptosis were observed in the lymphocyte population derived from either SF or PB. CONCLUSION: In RA patients, both etanercept and infliximab are able to induce cell type-specific apoptosis in the monocyte/macrophage population. This suggests a potential pathway that would account for the diminished synovial inflammation and the decreased numbers of synovial macrophages evident after TNF blockade. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/15641091/Evidence_that_anti_tumor_necrosis_factor_therapy_with_both_etanercept_and_infliximab_induces_apoptosis_in_macrophages_but_not_lymphocytes_in_rheumatoid_arthritis_joints:_extended_report_ L2 - https://doi.org/10.1002/art.20764 DB - PRIME DP - Unbound Medicine ER -