Analysis of the inflammatory cytokine network among TNFα, IL-1β, IL-1 receptor antagonist, and IL-8 in LPS-induced rabbit arthritis

Akihiro Matsukawa, Teizo Yoshimura, Kazuhiko Miyamoto, Susumu Ohkawara, Masaru Yoshinaga

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

We investigated the cytokine network in rabbit lipopolysaccharide (LPS)- induced arthritis, using inhibitors against homologous TNFα, IL-1β, and IL- 8. Rabbits were intraarticularly injected with LPS (10 ng) and cytokine inhibitors (10μg each), and the concentrations of each cytokine in the synovial fluids were measured. Maximum levels of TNFα and IL-8 were detected at 2 hours after LPS-injection, whereas IL-1β and IL-1 receptor antagonist (IL-1Ra) were detected at 6 and 9 hours, respectively. By immunohistochemistry, synovial lining cells were positive for TNFα and IL- 8, and infiltrating leukocytes were positive for IL-1α and IL-1Ra. The effects of cytokine inhibitors on the release of each cytokine were then investigated. The maximum levels of TNFα and IL-8 were not affected by blocking the activities of other cytokines. In contrast, the peak concentration of IL-1β was reduced by anti-TNFα monoclonal Ab (mAb), IL- 1Ra or anti-IL-8 IgG. Peak concentrations of IL-1Ra were reduced by anti- TNFα mAb or anti-IL-8 IgG. Anti-TNFα mAb, IL-1Ra, and anti-IL-8 IgG reduced the recruitment of leukocytes into the joint cavity, and the effect of anti- IL-8 IgG was less than that of anti-TNFα mAb plus IL-1Ra. The initial phase of the leukocyte influx was not inhibited. These results provide new evidence that IL-8 as well as TNFα are the most proximal cytokines and induce subsequent production of IL-1β and IL-1Ra. The data also raise the possibility that factor(s) other than IL-8 may be involved in the leukocyte influx in LPS-induced arthritis.

Original languageEnglish
Pages (from-to)629-638
Number of pages10
JournalLaboratory Investigation
Volume76
Issue number5
Publication statusPublished - May 1997
Externally publishedYes

Fingerprint

Interleukin-1 Receptors
Interleukin-8
Interleukin-1
Arthritis
Lipopolysaccharides
Cytokines
Rabbits
Leukocytes
Immunoglobulin G
Interleukin 1 Receptor Antagonist Protein
Synovial Fluid
Joints
Immunohistochemistry
Injections

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Analysis of the inflammatory cytokine network among TNFα, IL-1β, IL-1 receptor antagonist, and IL-8 in LPS-induced rabbit arthritis. / Matsukawa, Akihiro; Yoshimura, Teizo; Miyamoto, Kazuhiko; Ohkawara, Susumu; Yoshinaga, Masaru.

In: Laboratory Investigation, Vol. 76, No. 5, 05.1997, p. 629-638.

Research output: Contribution to journalArticle

@article{20b91f61a6be440a9fa08de112d5a09e,
title = "Analysis of the inflammatory cytokine network among TNFα, IL-1β, IL-1 receptor antagonist, and IL-8 in LPS-induced rabbit arthritis",
abstract = "We investigated the cytokine network in rabbit lipopolysaccharide (LPS)- induced arthritis, using inhibitors against homologous TNFα, IL-1β, and IL- 8. Rabbits were intraarticularly injected with LPS (10 ng) and cytokine inhibitors (10μg each), and the concentrations of each cytokine in the synovial fluids were measured. Maximum levels of TNFα and IL-8 were detected at 2 hours after LPS-injection, whereas IL-1β and IL-1 receptor antagonist (IL-1Ra) were detected at 6 and 9 hours, respectively. By immunohistochemistry, synovial lining cells were positive for TNFα and IL- 8, and infiltrating leukocytes were positive for IL-1α and IL-1Ra. The effects of cytokine inhibitors on the release of each cytokine were then investigated. The maximum levels of TNFα and IL-8 were not affected by blocking the activities of other cytokines. In contrast, the peak concentration of IL-1β was reduced by anti-TNFα monoclonal Ab (mAb), IL- 1Ra or anti-IL-8 IgG. Peak concentrations of IL-1Ra were reduced by anti- TNFα mAb or anti-IL-8 IgG. Anti-TNFα mAb, IL-1Ra, and anti-IL-8 IgG reduced the recruitment of leukocytes into the joint cavity, and the effect of anti- IL-8 IgG was less than that of anti-TNFα mAb plus IL-1Ra. The initial phase of the leukocyte influx was not inhibited. These results provide new evidence that IL-8 as well as TNFα are the most proximal cytokines and induce subsequent production of IL-1β and IL-1Ra. The data also raise the possibility that factor(s) other than IL-8 may be involved in the leukocyte influx in LPS-induced arthritis.",
author = "Akihiro Matsukawa and Teizo Yoshimura and Kazuhiko Miyamoto and Susumu Ohkawara and Masaru Yoshinaga",
year = "1997",
month = "5",
language = "English",
volume = "76",
pages = "629--638",
journal = "Laboratory Investigation",
issn = "0023-6837",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Analysis of the inflammatory cytokine network among TNFα, IL-1β, IL-1 receptor antagonist, and IL-8 in LPS-induced rabbit arthritis

AU - Matsukawa, Akihiro

AU - Yoshimura, Teizo

AU - Miyamoto, Kazuhiko

AU - Ohkawara, Susumu

AU - Yoshinaga, Masaru

PY - 1997/5

Y1 - 1997/5

N2 - We investigated the cytokine network in rabbit lipopolysaccharide (LPS)- induced arthritis, using inhibitors against homologous TNFα, IL-1β, and IL- 8. Rabbits were intraarticularly injected with LPS (10 ng) and cytokine inhibitors (10μg each), and the concentrations of each cytokine in the synovial fluids were measured. Maximum levels of TNFα and IL-8 were detected at 2 hours after LPS-injection, whereas IL-1β and IL-1 receptor antagonist (IL-1Ra) were detected at 6 and 9 hours, respectively. By immunohistochemistry, synovial lining cells were positive for TNFα and IL- 8, and infiltrating leukocytes were positive for IL-1α and IL-1Ra. The effects of cytokine inhibitors on the release of each cytokine were then investigated. The maximum levels of TNFα and IL-8 were not affected by blocking the activities of other cytokines. In contrast, the peak concentration of IL-1β was reduced by anti-TNFα monoclonal Ab (mAb), IL- 1Ra or anti-IL-8 IgG. Peak concentrations of IL-1Ra were reduced by anti- TNFα mAb or anti-IL-8 IgG. Anti-TNFα mAb, IL-1Ra, and anti-IL-8 IgG reduced the recruitment of leukocytes into the joint cavity, and the effect of anti- IL-8 IgG was less than that of anti-TNFα mAb plus IL-1Ra. The initial phase of the leukocyte influx was not inhibited. These results provide new evidence that IL-8 as well as TNFα are the most proximal cytokines and induce subsequent production of IL-1β and IL-1Ra. The data also raise the possibility that factor(s) other than IL-8 may be involved in the leukocyte influx in LPS-induced arthritis.

AB - We investigated the cytokine network in rabbit lipopolysaccharide (LPS)- induced arthritis, using inhibitors against homologous TNFα, IL-1β, and IL- 8. Rabbits were intraarticularly injected with LPS (10 ng) and cytokine inhibitors (10μg each), and the concentrations of each cytokine in the synovial fluids were measured. Maximum levels of TNFα and IL-8 were detected at 2 hours after LPS-injection, whereas IL-1β and IL-1 receptor antagonist (IL-1Ra) were detected at 6 and 9 hours, respectively. By immunohistochemistry, synovial lining cells were positive for TNFα and IL- 8, and infiltrating leukocytes were positive for IL-1α and IL-1Ra. The effects of cytokine inhibitors on the release of each cytokine were then investigated. The maximum levels of TNFα and IL-8 were not affected by blocking the activities of other cytokines. In contrast, the peak concentration of IL-1β was reduced by anti-TNFα monoclonal Ab (mAb), IL- 1Ra or anti-IL-8 IgG. Peak concentrations of IL-1Ra were reduced by anti- TNFα mAb or anti-IL-8 IgG. Anti-TNFα mAb, IL-1Ra, and anti-IL-8 IgG reduced the recruitment of leukocytes into the joint cavity, and the effect of anti- IL-8 IgG was less than that of anti-TNFα mAb plus IL-1Ra. The initial phase of the leukocyte influx was not inhibited. These results provide new evidence that IL-8 as well as TNFα are the most proximal cytokines and induce subsequent production of IL-1β and IL-1Ra. The data also raise the possibility that factor(s) other than IL-8 may be involved in the leukocyte influx in LPS-induced arthritis.

UR - http://www.scopus.com/inward/record.url?scp=0030971141&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030971141&partnerID=8YFLogxK

M3 - Article

C2 - 9166282

AN - SCOPUS:0030971141

VL - 76

SP - 629

EP - 638

JO - Laboratory Investigation

JF - Laboratory Investigation

SN - 0023-6837

IS - 5

ER -