Infliximab and etanercept have distinct actions but similar effects on cytokine profiles in rheumatoid arthritis

Masaru Takeshita, Katsuya Suzuki, Jun Kikuchi, Keisuke Izumi, Takahiko Kurasawa, Keiko Yoshimoto, Koichi Amano, Tsutomu Takeuchi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objective: Pro-inflammatory cytokines, especially TNFα, play a central role in the pathogenesis of rheumatoid arthritis (RA). The available TNF inhibitors are only slightly different from one another in terms of clinical efficacy, at least at the group level, but their structures and modes of action are not identical. Infliximab (IFX) and etanercept (ETN) differ in their ability to induce antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, and in their ability to bind TNFβ. The purpose of our study was to elucidate the different cytokine pathways through which these two drugs enact their clinical efficacy. Methods: Serum from 44 RA patients treated with IFX and 24 patients treated with ETN was studied. All patients had been given these biologics at identical dosages and intervals for one year. The concentrations of 11 inflammatory cytokines and their receptors (IL-1β, IL-2, IL-6, IL-6R, IL-8, IL-10, IL-12, TNFα, TNFβ, IFNγ, and GM-CSF) were measured at weeks 0, 22, and 54 using a high-sensitivity electro-chemiluminescence assay. Cytokine profiles were analyzed along with clinical efficacy. Results: IL-6 was significantly decreased in the ETN. +. MTX and IFX. +. MTX groups, although not in the ETN-only group; this change was consistent with changes in disease activity. IFNγ was gradually increased only in the non-remission subgroup of the IFX group, and not at all in the ETN group. TNFβ increased after starting IFX regardless of clinical efficacy. Conclusion: IL-6 inhibition is a pathway affected by both IFX and ETN. In addition, IFNγ increase is a distinctive feature of the inefficacy of IFX.

Original languageEnglish
Pages (from-to)222-227
Number of pages6
JournalCytokine
Volume75
Issue number2
DOIs
Publication statusPublished - 2015 Oct 1

Fingerprint

Rheumatoid Arthritis
Cytokines
Interleukin-6
Cytotoxicity
Cytokine Receptors
Chemiluminescence
Interleukin-12
Granulocyte-Macrophage Colony-Stimulating Factor
Luminescence
Infliximab
Etanercept
Biological Products
Interleukin-8
Interleukin-1
Interleukin-10
Interleukin-2
Assays
Antibodies
Serum
Pharmaceutical Preparations

Keywords

  • Etanercept
  • Infliximab
  • Interferon-gamma
  • Interleukin-6
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology
  • Biochemistry
  • Molecular Biology

Cite this

Infliximab and etanercept have distinct actions but similar effects on cytokine profiles in rheumatoid arthritis. / Takeshita, Masaru; Suzuki, Katsuya; Kikuchi, Jun; Izumi, Keisuke; Kurasawa, Takahiko; Yoshimoto, Keiko; Amano, Koichi; Takeuchi, Tsutomu.

In: Cytokine, Vol. 75, No. 2, 01.10.2015, p. 222-227.

Research output: Contribution to journalArticle

Takeshita, Masaru ; Suzuki, Katsuya ; Kikuchi, Jun ; Izumi, Keisuke ; Kurasawa, Takahiko ; Yoshimoto, Keiko ; Amano, Koichi ; Takeuchi, Tsutomu. / Infliximab and etanercept have distinct actions but similar effects on cytokine profiles in rheumatoid arthritis. In: Cytokine. 2015 ; Vol. 75, No. 2. pp. 222-227.
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T1 - Infliximab and etanercept have distinct actions but similar effects on cytokine profiles in rheumatoid arthritis

AU - Takeshita, Masaru

AU - Suzuki, Katsuya

AU - Kikuchi, Jun

AU - Izumi, Keisuke

AU - Kurasawa, Takahiko

AU - Yoshimoto, Keiko

AU - Amano, Koichi

AU - Takeuchi, Tsutomu

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N2 - Objective: Pro-inflammatory cytokines, especially TNFα, play a central role in the pathogenesis of rheumatoid arthritis (RA). The available TNF inhibitors are only slightly different from one another in terms of clinical efficacy, at least at the group level, but their structures and modes of action are not identical. Infliximab (IFX) and etanercept (ETN) differ in their ability to induce antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, and in their ability to bind TNFβ. The purpose of our study was to elucidate the different cytokine pathways through which these two drugs enact their clinical efficacy. Methods: Serum from 44 RA patients treated with IFX and 24 patients treated with ETN was studied. All patients had been given these biologics at identical dosages and intervals for one year. The concentrations of 11 inflammatory cytokines and their receptors (IL-1β, IL-2, IL-6, IL-6R, IL-8, IL-10, IL-12, TNFα, TNFβ, IFNγ, and GM-CSF) were measured at weeks 0, 22, and 54 using a high-sensitivity electro-chemiluminescence assay. Cytokine profiles were analyzed along with clinical efficacy. Results: IL-6 was significantly decreased in the ETN. +. MTX and IFX. +. MTX groups, although not in the ETN-only group; this change was consistent with changes in disease activity. IFNγ was gradually increased only in the non-remission subgroup of the IFX group, and not at all in the ETN group. TNFβ increased after starting IFX regardless of clinical efficacy. Conclusion: IL-6 inhibition is a pathway affected by both IFX and ETN. In addition, IFNγ increase is a distinctive feature of the inefficacy of IFX.

AB - Objective: Pro-inflammatory cytokines, especially TNFα, play a central role in the pathogenesis of rheumatoid arthritis (RA). The available TNF inhibitors are only slightly different from one another in terms of clinical efficacy, at least at the group level, but their structures and modes of action are not identical. Infliximab (IFX) and etanercept (ETN) differ in their ability to induce antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, and in their ability to bind TNFβ. The purpose of our study was to elucidate the different cytokine pathways through which these two drugs enact their clinical efficacy. Methods: Serum from 44 RA patients treated with IFX and 24 patients treated with ETN was studied. All patients had been given these biologics at identical dosages and intervals for one year. The concentrations of 11 inflammatory cytokines and their receptors (IL-1β, IL-2, IL-6, IL-6R, IL-8, IL-10, IL-12, TNFα, TNFβ, IFNγ, and GM-CSF) were measured at weeks 0, 22, and 54 using a high-sensitivity electro-chemiluminescence assay. Cytokine profiles were analyzed along with clinical efficacy. Results: IL-6 was significantly decreased in the ETN. +. MTX and IFX. +. MTX groups, although not in the ETN-only group; this change was consistent with changes in disease activity. IFNγ was gradually increased only in the non-remission subgroup of the IFX group, and not at all in the ETN group. TNFβ increased after starting IFX regardless of clinical efficacy. Conclusion: IL-6 inhibition is a pathway affected by both IFX and ETN. In addition, IFNγ increase is a distinctive feature of the inefficacy of IFX.

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KW - Interferon-gamma

KW - Interleukin-6

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