The association of cytokines with disease activity and damage scores in systemic lupus erythematosus patients.
OBJECTIVE
The aim of this study was to explore the role of cytokines in the pathogenesis of SLE in a genetically homogeneous Caucasian SLE patient population.


METHODS
Serum levels of the following cytokines were determined by ELISA in SLE patients (diagnosed as per ACR diagnostic criteria): IL-1β, IL-10, IL-12p70 and TNF-α. Demographic data, disease activity as per the SLEDAI and damage scores (SLICC) at the 5-year follow-up were calculated.


RESULTS
Enhanced production of TNF-α, IL-1 and IL-10 were observed in SLE patients compared with controls. A strong positive correlation was seen between levels of IL-12p70 and IL-10. In addition, IL-10, TNF-α and IL-1 demonstrated a significant relationship with disease activity. Interestingly, elevated levels of IL-10 were observed in SLE patients with CNS involvement while patients with elevated levels of TNF-α were more likely to have renal involvement and sustain damage over the follow-up period. Additionally, the ratio of all cytokines assayed to IL-12p70 levels were significantly higher in SLE patients when compared with controls, with an association seen between damage accrual and the IL-1β/IL-12p70 ratio (r = 0.431, P = 0.003), IL-10/IL-12p70 ratio (r = 0.351, P = 0.018) and TNF-α/IL-12p70 ratio (r = 0.33, P = 0.028). When the respective ratios were analysed for organ-specific disease, significant differences were observed for the IL-1β/IL-12p70 ratio (0.79 vs 0.47, P = 0.036), IL-10/IL-12p70 ratio (4.29 vs 1.87, P = 0.018) and TNF-α/IL-12p70 ratio (7.49 vs 5.21, P = 0.018) with respect to renal involvement.


CONCLUSIONS
Increased levels of a number of immunomodulatory cytokines relative to IL-12p70 in this Caucasian SLE patient population are seen in patients with renal involvement and are associated with increased accrual of damage at the 5-year follow-up.
Department of Rheumatology, Beaumont Hospital, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Department of Rheumatology, St James Hospital and Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland.Department of Rheumatology, Beaumont Hospital, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Department of Rheumatology, St James Hospital and Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland.
Eoghan M
EM
McCarthy
Department of Rheumatology, Beaumont Hospital, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Department of Rheumatology, St James Hospital and Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland.
Siobhán
S
Smith
Department of Rheumatology, Beaumont Hospital, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Department of Rheumatology, St James Hospital and Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland.
Ruth Z
RZ
Lee
Department of Rheumatology, Beaumont Hospital, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Department of Rheumatology, St James Hospital and Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland.
Gaye
G
Cunnane
Department of Rheumatology, Beaumont Hospital, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Department of Rheumatology, St James Hospital and Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland.
Michele F
MF
Doran
Department of Rheumatology, Beaumont Hospital, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Department of Rheumatology, St James Hospital and Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland.
Suzanne
S
Donnelly
Department of Rheumatology, Beaumont Hospital, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Department of Rheumatology, St James Hospital and Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland.
Donough
D
Howard
Department of Rheumatology, Beaumont Hospital, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Department of Rheumatology, St James Hospital and Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland.
Paul
P
O'Connell
Department of Rheumatology, Beaumont Hospital, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Department of Rheumatology, St James Hospital and Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland.
Grainne
G
Kearns
Department of Rheumatology, Beaumont Hospital, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Department of Rheumatology, St James Hospital and Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland.
Joan
J
Ní Gabhann
Department of Rheumatology, Beaumont Hospital, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Department of Rheumatology, St James Hospital and Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland. cjefferies@rcsi.ie.
Caroline A
CA
Jefferies
D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12
cytokines; damage accrual; disease activity; systemic lupus erythematosus