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 systemi c lupus erythematosus (SLE), prior to the initiation of treatment with corticosteroids. Methods. Using sensitive radioimmunoassays, interleu kin-4 (IL-4), IL-10, IL-12 p40, tumor necrosis factor alpha (TNF alpha ), interferon-gamma (IFN gamma), and granulocyte-macrophage colony-sti mulating factor (GM-CSF) released into the culture supernatants of var ious unstimulated and stimulated blood mononuclear cell populations fr om 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 decrease d amounts of IL-12 following stimulation. Lymphocyte-enriched cells in SLE produced decreased amounts of IFN gamma and TNF alpha following s timulation. 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 cont rols, but not in SLE patients. Increased IL-4 production or abnormalit ies in GM-CSF production were not observed. Conclusion. This study sug gests that el en 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 betwee n IL-IO and IL-12. A contributory role of dysfunctional CD8+ cells is suggested.