Interleukin 10 (IL-10), not IL-4 or interferon-gamma production, correlates with progression of joint destruction in rheumatoid arthritis.
OBJECTIVE
Both interleukin 4 (IL-4) and IL-10, separately and in combination, and under in vitro and in vivo conditions in animals, have been reported to inhibit characteristics of rheumatoid arthritis (RA) and experimentally induced arthritis. We investigated if IL-10 and IL-4 production, as well as interferon-gamma (IFN-gamma) production, opposing IL-4, were related to RA disease variables. A method was chosen to exclude the influence of age and disease duration.


METHODS
We selected RA patients with mild and severe disease. Inclusion criteria were erythrocyte sedimentation rate (ESR) < or = 28 mm/h and > or = 50, C-reactive protein (CRP) < or = 20 and > or = 30, Thompson joint score < or = 60 and > or = 100 and radiographic joint damage score, Sharp score < or = 30 and > or = 40. Age and disease duration were restricted: 30 to 70 years and 5 to 15 years, respectively. Peripheral blood mononuclear cells were isolated and the ex vivo 48 h production of T cell IL-10, IL-4, and IFN-gamma (after CD3-CD28 stimulation) was assessed and was correlated to clinical variables.


RESULTS
Only IL-10 production differed significantly between the 2 groups of RA patients, being highest in the "mild" group. Taking all patients together, a strong negative correlation was found between IL-10 production and radiographic joint damage (r = -0.53, p < 0.001) as well as progression of joint damage (r = -0.56, p < 0.0001). Similar negative correlations, although less powerful, were found between IL-10 production and ESR, CRP, and Thompson joint score. No correlation was found for IFN-gamma, IL-4, or the ratio of the 2 with disease activity variables or joint damage.


CONCLUSIONS
The findings suggest that the high IL-10 production found in patients with RA may be protective, especially against progression of joint destruction in RA.
Verhoef
C M
CM
Department of Rheumatology and Clinical Immunology, University Medical Center of Utrecht, The Netherlands. c.verhoef@digd.azu.nl
van Roon
J A
JA
Vianen
M E
ME
Bijlsma
J W
JW
Lafeber
F P
FP
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D015415:Biomarkers / Q000032:analysis; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000032:analysis / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D017678:Sex Distribution; D018709:Statistics, Nonparametric
D015415:Biomarkers; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma