In vivo study of pro-inflammatory cytokine changes in serum and synovial fluid during treatment with celecoxib and etoricoxib and correlation with VAS pain change and synovial membrane penetration index in patients with inflammatory arthritis
- PMID: 32185252
- PMCID: PMC7045925
- DOI: 10.31138/mjr.28.1.33
In vivo study of pro-inflammatory cytokine changes in serum and synovial fluid during treatment with celecoxib and etoricoxib and correlation with VAS pain change and synovial membrane penetration index in patients with inflammatory arthritis
Abstract
Objectives: To determine the impact of celecoxib and etoricoxib therapy on serum and synovial fluid levels of IL-1β, IL-6, TNF-α, sTNFR1, sTNFR2 and IL-1Ra in patients with inflammatory arthritis. To determine the correlation between cytokine changes and synovial membrane penetration index of the study drugs, and pain VAS change.
Methods: Fifty-one patients with inflammatory synovial fluid accumulation in a knee joint (33 women), randomized on 3 groups of 17 each: 100 mg b.i.d. celecoxib treated group, 90 mg o.d. etoricoxib treated group, and the control group with no NSAID treatment. Cytokines serum and synovial fluid levels as well as membrane penetration index were assessed prior and after treatment.
Results: Celecoxib led to decrease of both synovial fluid and serum levels of IL-6 (p=0.017 and p=0.003, respectively). In the etoricoxib treated group synovial fluid IL-6 concentration was significantly decreased after treatment (p=0.019). Correlating the study drugs penetration index with the change of cytokines and their receptors levels, positive correlation was found with the reduction of synovial fluid IL-1β for the celecoxib (p=0.032) and with the increase of synovial fluid sTNFR1 for the etoricoxib group (p=0.028). Pain VAS reduction was positively correlated with decrease of synovial fluid IL-1β (p=0.041) and IL-6 levels (p<0.005) and negative with synovial fluid sTNFR1 changes (p=0.045) in celecoxib group, and negative with serum TNF-α decrease (p=0.044) in the etoricoxib group.
Conclusion: Our results suggest that celecoxib and etoricoxib inhibit the inflammatory cytokines, mostly in synovial fluid but also in serum, causing through this mechanism, decrease of inflammation, irrespective to COX-2 inhibition.
Keywords: celecoxib; cytokines; etoricoxib; inflammatory arthritis; synovial fluid.
© 2017 The Mediterranean Journal of Rheumatology (MJR).
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References
-
- Vane J R, Flower R J, Botting R M. History of aspirin and its mechanism of action. Stroke 1990;21:IV12–23. - PubMed
-
- Niederberger E, Tegeder I, Vetter G, Schmidtko A, Schmidt H, Euchenhofer C, et al. Celecoxib loses its anti-inflammatory efficacy at high doses through activation of NF-kappaB. FASEB J 2001;15:1622–4. - PubMed
-
- Kim S H, Song S H, Kim S G, Chun K S, Lim S Y, Na H K, et al. Celecoxib induces apoptosis in cervical cancer cells independent of cyclooxygenase using NF-kappaB as a possible target. J Cancer Res Clin Oncol 2004;130:551–60. - PubMed
-
- Monakier D, Mates M, Klutstein M W, Balkin J A, Rudensky B, Meerkin D, et al. Rofecoxib, a COX-2 inhibitor, lowers C-reactive protein and interleukin-6 levels in patients with acute coronary syndromes. Chest 2004;125:1610–5. - PubMed
-
- Bogaty P, Brophy J M, Noel M, Boyer L, Simard S, Bertrand F, et al. Impact of prolonged cyclooxygenase-2 inhibition on inflammatory markers and endothelial function in patients with ischemic heart disease and raised C-reactive protein: a randomized placebo-controlled study. Circulation 2004;110:934–9. - PubMed
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