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Systemic cytokine levels and the effects of etanercept in TNF receptor-associated periodic syndrome (TRAPS) involving a C33Y mutation in TNFRSF1A.
Rheumatology (Oxford) 2006; 45(1):31-7R

Abstract

OBJECTIVE

To investigate the levels of the pro-inflammatory cytokines IL-6, TNF-alpha, IL-1beta, IL-8, IL-10 and IL-12p70 in the plasma of patients with TNF receptor-associated periodic syndrome (TRAPS) in relation to CRP levels and treatment with etanercept.

METHODS

Cytokine concentrations were measured in sequential plasma samples obtained from eight patients with a C33Y mutation in TNFRSF1A and diagnosed with TRAPS, using cytokine bead array. The TRAPS samples were compared with samples from normal controls and rheumatoid arthritis patients.

RESULTS

Levels of IL-6 were significantly elevated in C33Y TRAPS patients and these correlated with CRP levels in some of the patients. IL-8 levels were also significantly elevated in the TRAPS patients. However, neither TNF-alpha nor IL-1beta demonstrated a similar increase. This differed from the patients with rheumatoid arthritis, for whom levels of IL-6, IL-8, TNF-alpha, IL-1beta and IL-10 were significantly elevated. The levels of detectable TNF-alpha in the TRAPS patients' plasma were elevated during etanercept treatment.

CONCLUSIONS

The cytokine profile of C33Y TRAPS differs from that of a typical autoimmune inflammatory condition such as rheumatoid arthritis, as only IL-6 and IL-8 were elevated in C33Y TRAPS patients, as distinct from a generalized elevation of pro-inflammatory cytokines. However, only some of the C33Y patients tested showed a relationship between elevated IL-6 and CRP. This is consistent with clinical observations that there is marked heterogeneity between individuals with TRAPS, including those in the same family cohort. Although etanercept has a therapeutic effect in some TRAPS patients, it induces increased plasma concentrations of TNF-alpha, possibly by increasing TNF-alpha stability.

Authors+Show Affiliations

Division of Immunology, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.No 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
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16287931

Citation

Nowlan, M L., et al. "Systemic Cytokine Levels and the Effects of Etanercept in TNF Receptor-associated Periodic Syndrome (TRAPS) Involving a C33Y Mutation in TNFRSF1A." Rheumatology (Oxford, England), vol. 45, no. 1, 2006, pp. 31-7.
Nowlan ML, Drewe E, Bulsara H, et al. Systemic cytokine levels and the effects of etanercept in TNF receptor-associated periodic syndrome (TRAPS) involving a C33Y mutation in TNFRSF1A. Rheumatology (Oxford). 2006;45(1):31-7.
Nowlan, M. L., Drewe, E., Bulsara, H., Esposito, N., Robins, R. A., Tighe, P. J., ... Todd, I. (2006). Systemic cytokine levels and the effects of etanercept in TNF receptor-associated periodic syndrome (TRAPS) involving a C33Y mutation in TNFRSF1A. Rheumatology (Oxford, England), 45(1), pp. 31-7.
Nowlan ML, et al. Systemic Cytokine Levels and the Effects of Etanercept in TNF Receptor-associated Periodic Syndrome (TRAPS) Involving a C33Y Mutation in TNFRSF1A. Rheumatology (Oxford). 2006;45(1):31-7. PubMed PMID: 16287931.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Systemic cytokine levels and the effects of etanercept in TNF receptor-associated periodic syndrome (TRAPS) involving a C33Y mutation in TNFRSF1A. AU - Nowlan,M L, AU - Drewe,E, AU - Bulsara,H, AU - Esposito,N, AU - Robins,R A, AU - Tighe,P J, AU - Powell,R J, AU - Todd,I, Y1 - 2005/11/15/ PY - 2005/11/17/pubmed PY - 2006/2/10/medline PY - 2005/11/17/entrez SP - 31 EP - 7 JF - Rheumatology (Oxford, England) JO - Rheumatology (Oxford) VL - 45 IS - 1 N2 - OBJECTIVE: To investigate the levels of the pro-inflammatory cytokines IL-6, TNF-alpha, IL-1beta, IL-8, IL-10 and IL-12p70 in the plasma of patients with TNF receptor-associated periodic syndrome (TRAPS) in relation to CRP levels and treatment with etanercept. METHODS: Cytokine concentrations were measured in sequential plasma samples obtained from eight patients with a C33Y mutation in TNFRSF1A and diagnosed with TRAPS, using cytokine bead array. The TRAPS samples were compared with samples from normal controls and rheumatoid arthritis patients. RESULTS: Levels of IL-6 were significantly elevated in C33Y TRAPS patients and these correlated with CRP levels in some of the patients. IL-8 levels were also significantly elevated in the TRAPS patients. However, neither TNF-alpha nor IL-1beta demonstrated a similar increase. This differed from the patients with rheumatoid arthritis, for whom levels of IL-6, IL-8, TNF-alpha, IL-1beta and IL-10 were significantly elevated. The levels of detectable TNF-alpha in the TRAPS patients' plasma were elevated during etanercept treatment. CONCLUSIONS: The cytokine profile of C33Y TRAPS differs from that of a typical autoimmune inflammatory condition such as rheumatoid arthritis, as only IL-6 and IL-8 were elevated in C33Y TRAPS patients, as distinct from a generalized elevation of pro-inflammatory cytokines. However, only some of the C33Y patients tested showed a relationship between elevated IL-6 and CRP. This is consistent with clinical observations that there is marked heterogeneity between individuals with TRAPS, including those in the same family cohort. Although etanercept has a therapeutic effect in some TRAPS patients, it induces increased plasma concentrations of TNF-alpha, possibly by increasing TNF-alpha stability. SN - 1462-0324 UR - https://www.unboundmedicine.com/medline/citation/16287931/Systemic_cytokine_levels_and_the_effects_of_etanercept_in_TNF_receptor_associated_periodic_syndrome__TRAPS__involving_a_C33Y_mutation_in_TNFRSF1A_ L2 - https://academic.oup.com/rheumatology/article-lookup/doi/10.1093/rheumatology/kei090 DB - PRIME DP - Unbound Medicine ER -