Decreased production of interleukin-12 and other Th1-type cytokines in patients with recent-onset systemic lupus erythematosus

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Abstract
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 α (TNFα), interferon‐γ (IFNγ), 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 IFNγ and TNFα 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 TNFα and IFNγ in controls, but not in SLE patients. Increased IL‐4 production or abnormalities in GM‐CSF production were not observed. Conclusion 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.