Long-term treatment with etanercept significantly reduces the number of proinflammatory cytokine-secreting peripheral blood mononuclear cells in patients with rheumatoid arthritis.
OBJECTIVE
To determine the influence of etanercept treatment on the number of peripheral blood mononuclear cells (PBMC) secreting immunoregulatory key cytokines and the correlation of these cell counts with treatment response in patients with rheumatoid arthritis (RA).


METHODS
Nineteen patients with RA were treated with etanercept as monotherapy. Frequencies of PBMC secreting cytokines were determined by ELISPOT analysis before and after 9 months of therapy and compared with values for healthy controls (HC). The clinical outcome was assessed as defined by the ACR criteria.


RESULTS
Fifteen patients fulfilled the ACR20, seven patients the ACR50 and two patients the ACR70 criteria. Initially elevated numbers of tumour necrosis factor-alpha- and interleukin (IL)-1beta-secreting PBMC were reduced to HC levels, and normal or low numbers of IL-6- and interferon-gamma (IFN-gamma)-secreting PBMC were reduced below HC levels. The number of IL-10-secreting PBMC did not differ from that in HC and did not change significantly over time. The pretreatment IFN-gamma:IL-10 ratio correlated to reduction in the tender and swollen joint counts.


CONCLUSIONS
Long-term treatment with etanercept in patients with RA significantly reduces the numbers of proinflammatory cytokine-secreting PBMC, while the number of IL-10-secreting cells is unaffected. Although the changes described did not affect the safety or efficacy of etanercept therapy, these alterations may account for the long-term systemic effects. The pretreatment IFN-gamma:IL-10 ratio may be of prognostic value in predicting the improvement in joint symptoms.
Schotte
H
H
Medizinische Klinik, Universitätsklinikum Münster, Germany. h.schotte@uni-muenster.de
Schlüter
B
B
Willeke
P
P
Mickholz
E
E
Schorat
M A
MA
Domschke
W
W
Gaubitz
M
M
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism*; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000032:analysis; D007375:Interleukin-1 / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008134:Long-Term Care / Q000379:methods; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D018501:Antirheumatic Agents; D016207:Cytokines; D007074:Immunoglobulin G; D007375:Interleukin-1; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D000068800:Etanercept