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Association of interleukin-18 expression with enhanced levels of both interleukin-1beta and tumor necrosis factor alpha in knee synovial tissue of patients with rheumatoid arthritis.
Arthritis Rheum. 2003 Feb; 48(2):339-47.AR

Abstract

OBJECTIVE

To examine the expression patterns of interkeukin-18 (IL-18) in synovial biopsy tissue of patients with rheumatoid arthritis (RA), and to determine whether expression of this primary cytokine is related to the expression of other cytokines and adhesion molecules and related to the degree of joint inflammation.

METHODS

Biopsy specimens of knee synovial tissue either without synovitis (n = 6) or with moderate or severe synovitis (n = 11 and n = 12, respectively) were obtained from 29 patients with active RA. Paraffin-embedded, snap-frozen sections were used for immunohistochemical detection of IL-18, tumor necrosis factor alpha (TNFalpha), IL-1beta, IL-12, and IL-17. Furthermore, adhesion molecules, such as intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin, and cell markers CD3, CD14, and CD68 were stained.

RESULTS

IL-18 staining was detectable in 80% of the RA patients, in both the lining and sublining of the knee synovial tissue. IL-18 expression in the synovial tissue was strongly correlated with the expression of IL-1beta (in the sublining r = 0.72, in the lining r = 0.71; both P < 0.0001) and TNFalpha (in the sublining r = 0.59, P < 0.0007, and in the lining r = 0.68, P < 0.0001). In addition, IL-18 expression in the sublining correlated with macrophage infiltration (r = 0.64, P < 0.0007) and microscopic inflammation scores (r = 0.78, P < 0.0001), and with the acute-phase reaction as measured by the erythrocyte sedimentation rate (r = 0.61, P < 0.0004). Interestingly, RA synovial tissue that coexpressed IL-18 and IL-12 demonstrated enhanced levels of the Th1-associated cytokine IL-17.

CONCLUSION

Our results show that expression of IL-18 is associated with that of IL-1beta and TNFalpha and with local inflammation in the synovial tissue of patients with RA. In addition, synovial IL-18 expression correlates with the acute-phase response. These data indicate that IL-18 is a primary proinflammatory cytokine in RA that drives the local production of IL-1beta and TNFalpha.

Authors+Show Affiliations

Rheumatology Research Laboratory, University Medical Center Nijmegen, Nijmegen, The Netherlands. l.joosten@reum.azn.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12571842

Citation

Joosten, Leo A B., et al. "Association of Interleukin-18 Expression With Enhanced Levels of Both Interleukin-1beta and Tumor Necrosis Factor Alpha in Knee Synovial Tissue of Patients With Rheumatoid Arthritis." Arthritis and Rheumatism, vol. 48, no. 2, 2003, pp. 339-47.
Joosten LA, Radstake TR, Lubberts E, et al. Association of interleukin-18 expression with enhanced levels of both interleukin-1beta and tumor necrosis factor alpha in knee synovial tissue of patients with rheumatoid arthritis. Arthritis Rheum. 2003;48(2):339-47.
Joosten, L. A., Radstake, T. R., Lubberts, E., van den Bersselaar, L. A., van Riel, P. L., van Lent, P. L., Barrera, P., & van den Berg, W. B. (2003). Association of interleukin-18 expression with enhanced levels of both interleukin-1beta and tumor necrosis factor alpha in knee synovial tissue of patients with rheumatoid arthritis. Arthritis and Rheumatism, 48(2), 339-47.
Joosten LA, et al. Association of Interleukin-18 Expression With Enhanced Levels of Both Interleukin-1beta and Tumor Necrosis Factor Alpha in Knee Synovial Tissue of Patients With Rheumatoid Arthritis. Arthritis Rheum. 2003;48(2):339-47. PubMed PMID: 12571842.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of interleukin-18 expression with enhanced levels of both interleukin-1beta and tumor necrosis factor alpha in knee synovial tissue of patients with rheumatoid arthritis. AU - Joosten,Leo A B, AU - Radstake,Timothy R D, AU - Lubberts,Erik, AU - van den Bersselaar,Liduine A M, AU - van Riel,Piet L C M, AU - van Lent,Peter L E M, AU - Barrera,Pilar, AU - van den Berg,Wim B, PY - 2003/2/7/pubmed PY - 2003/3/14/medline PY - 2003/2/7/entrez SP - 339 EP - 47 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 48 IS - 2 N2 - OBJECTIVE: To examine the expression patterns of interkeukin-18 (IL-18) in synovial biopsy tissue of patients with rheumatoid arthritis (RA), and to determine whether expression of this primary cytokine is related to the expression of other cytokines and adhesion molecules and related to the degree of joint inflammation. METHODS: Biopsy specimens of knee synovial tissue either without synovitis (n = 6) or with moderate or severe synovitis (n = 11 and n = 12, respectively) were obtained from 29 patients with active RA. Paraffin-embedded, snap-frozen sections were used for immunohistochemical detection of IL-18, tumor necrosis factor alpha (TNFalpha), IL-1beta, IL-12, and IL-17. Furthermore, adhesion molecules, such as intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin, and cell markers CD3, CD14, and CD68 were stained. RESULTS: IL-18 staining was detectable in 80% of the RA patients, in both the lining and sublining of the knee synovial tissue. IL-18 expression in the synovial tissue was strongly correlated with the expression of IL-1beta (in the sublining r = 0.72, in the lining r = 0.71; both P < 0.0001) and TNFalpha (in the sublining r = 0.59, P < 0.0007, and in the lining r = 0.68, P < 0.0001). In addition, IL-18 expression in the sublining correlated with macrophage infiltration (r = 0.64, P < 0.0007) and microscopic inflammation scores (r = 0.78, P < 0.0001), and with the acute-phase reaction as measured by the erythrocyte sedimentation rate (r = 0.61, P < 0.0004). Interestingly, RA synovial tissue that coexpressed IL-18 and IL-12 demonstrated enhanced levels of the Th1-associated cytokine IL-17. CONCLUSION: Our results show that expression of IL-18 is associated with that of IL-1beta and TNFalpha and with local inflammation in the synovial tissue of patients with RA. In addition, synovial IL-18 expression correlates with the acute-phase response. These data indicate that IL-18 is a primary proinflammatory cytokine in RA that drives the local production of IL-1beta and TNFalpha. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/12571842/Association_of_interleukin_18_expression_with_enhanced_levels_of_both_interleukin_1beta_and_tumor_necrosis_factor_alpha_in_knee_synovial_tissue_of_patients_with_rheumatoid_arthritis_ L2 - https://doi.org/10.1002/art.10814 DB - PRIME DP - Unbound Medicine ER -