Defective monocyte production of, and T lymphocyte response to, interleukin-1 in the peripheral blood of patients with systemic lupus erythematosus.

Interleukin-1 (IL-1) is a monocyte product with diverse amplifying effects on immune cell reactions. We have studied 16 untreated SLE patients to determine the production of IL-1 by their monocytes under the stimulus of E. Coli lipopolysaccharide (LPS) or phorbol myristate acetate (PMA) and measured by the capacity of their supernatants to augment normal autologous mixed lymphocyte cultures (AMLR) or to replace accessory cells in Con A-induced proliferation of T lymphocytes. Concurrently, we studied the response of T lymphocytes from these same patients to IL-1 by its capacity to increase the percentage of stable E rosette forming cells and by the enhancement of T cell proliferation in AMLR. Monocytes from SLE patients produced significantly less IL-1 activity than those of age matched controls, regardless of the stimulus (LPS or PMA), as well as of the indicator system. All patients with active disease and seven of the 10 patients with inactive disease had decreased production of IL-1 activity as determined by at least one method. Response of T lymphocytes from SLE patients to IL-1 produced by normal monocytes was also found decreased as compared to normals. This defect was more marked in the T cells from patients with active than in those of patients with inactive disease. These findings indicate that the immunoregulatory disturbance that SLE patients have encompasses monocytes as well as T and B lymphocytes and suggest that the defect is either multicentric or originates in the stem cell.