Decreased production of interleukin-12 and other Th1-type cytokines in patients with recent-onset systemic lupus erythematosus.
OBJECTIVE
To determine the profile of Th1-type and Th2-type cytokines produced by mononuclear cells from patients with recent-onset systemic lupus erythematosus (SLE), prior to the initiation of treatment with corticosteroids.


METHODS
Using sensitive radioimmunoassays, interleukin-4 (IL-4), IL-10, IL-12 p40, tumor necrosis factor alpha (TNF alpha), interferon-gamma (IFN gamma), and granulocyte-macrophage colony-stimulating factor (GM-CSF) released into the culture supernatants of various unstimulated and stimulated blood mononuclear cell populations from 10 SLE patients was assessed in comparison with 10 matched healthy controls studied in parallel.


RESULTS
In early SLE, monocyte-enriched cells constitutively produced increased amounts of IL-10 and decreased amounts of IL-12 following stimulation. Lymphocyte-enriched cells in SLE produced decreased amounts of IFN gamma and TNF alpha following stimulation. In "rested" cells, these defects were accentuated and a defect in IL-12 production was suggested. Depletion studies suggested that CD8+ cells were a major source of TNF alpha and IFN gamma in controls, but not in SLE patients. Increased IL-4 production or abnormalities in GM-CSF production were not observed.


CONCLUSIONS
This study suggests that even early in the course of SLE, monocyte production of IL-10 is increased and that of IL-12 is decreased. Decreased production of Th1-type cytokines in SLE may be secondary to this imbalance between IL-10 and IL-12. A contributory role of dysfunctional CD8+ cells is suggested.
Horwitz
D A
DA
University of Southern California School of Medicine, Los Angeles 90033, USA.
Gray
J D
JD
Behrendsen
S C
SC
Kubin
M
M
Rengaraju
M
M
Ohtsuka
K
K
Trinchieri
G
G
D000328:Adult; D002478:Cells, Cultured; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D008213:Lymphocyte Activation; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011863:Radioimmunoassay; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor