Cytokine production, serum levels and disease activity in systemic lupus erythematosus.
OBJECTIVE
T cell abnormalities, B cell hyperactivity and abnormal cytokine production have been implicated to be of pathogenic importance in systemic lupus erythematosus (SLE). The aim of this study was to investigate if ongoing production and serum levels of type 1 and 2 cytokines reflect disease activity and the presence of organ manifestations.


METHODS
Fifty-two SLE patients and 29 healthy individuals were investigated. Blood samples were collected for assessment of anti-ds DNA antibodies, cytokine production and serum cytokine levels. Disease activity was simultaneously assessed using the Systemic Lupus Activity Measure (SLAM) index and SLE Disease Activity Index (SLEDAI). ELISPOT analysis of freshly isolated peripheral blood mononuclear cells (PBMC) was used to estimate the production of cytokines (gamma-interferon (IFN-gamma), interleukin-4 (IL-4), IL-6 and IL-10) using both unstimulated cells and cells stimulated with the T cell mitogen phytohaemagglutinin (PHA). Serum levels of IL-10 were determined using an ELISA method, serum levels of IL-6 were determined using a bioassay and anti-ds DNA antibodies were analysed by immunofluorescence.


RESULTS
The SLE patient group had significantly increased numbers of cells spontaneously producing IL-10 and IL-6 as compared to healthy controls (P = 0.01 and 0.03, respectively). The number of cells producing IL-10 and IL-6 after PHA-stimulation was also increased in SLE patients (P = 0.01 and < 0.0004, respectively). Serum IL-10 and IL-6 levels were also significantly increased in SLE patients (P < 0.0004 and 0.0005, respectively). Serum IL-10 levels correlated with the titre of anti-ds DNA antibodies in the patients. No correlation was found between disease activity or clinical profiles and the production or serum levels of cytokines except for a weak correlation (not statistically significant) between levels of IL-10 in the sera and disease activity as measured by the SLEDAI but not by the SLAM index.


CONCLUSIONS
Our results confirm earlier reports that SLE patients have an increased production as well as increased serum levels of the type 2 cytokines IL-10 and IL-6. We found no significant correlation between IL-6 and IL-10 and disease activity or clinical profiles. Serum IL-10 levels correlated with the titre of anti-ds DNA antibodies in the SLE patients. In summary, our result indicate that the increased IL-10 production in SLE could be constitutive.
Gröndal
G
G
Department of Rheumatology, Karolinska Hospital, Stockholm, Sweden.
Gunnarsson
I
I
Rönnelid
J
J
Rogberg
S
S
Klareskog
L
L
Lundberg
I
I
D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood; D004247:DNA / Q000276:immunology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism
D000974:Antibodies, Antinuclear; D015850:Interleukin-6; D016753:Interleukin-10; D004247:DNA