Morris Ziff

LYMPHOKINES IN RHEUMATOID SYNOVITIS

In antigen-induced experimental arthritis of rabbits, a macrophage migration inhibitory factor was released from the inflamed synovial tissues. A migration inhibitory factor, blastogenic factor, and B-cell-stimulating factor were also found in human rheumatoid synovial fluids and culture supernatants of rheumatoid tissue explants. Joint fluids from patients with inflammatory conditions other than RA sometimes also displayed these activities. OA fluids were usually inactive. At present, little is known of the origin or role in vivo of the lymphokine-like activities observed in the joints of rheumatoid patients. In related experiments, injection of lymphokine-rich antigen-free lymphocyte supernatants into normal rabbit knee joints produced a synovitis characterized by lining layer hyperplasia and infiltration of the sublining layer by macrophages. The lymphocytic and plasmacytic components seen in active antigen-induced synovitis were absent. It seems likely that some of the changes observed in active chronic synovitis are mediated by soluble factors of the lymphokine variety.

Suppression by thymosin of pokeweed mitogen-induced differentiation of human B cells

Abstract Using an immunofluorescent method, the thymic hormone thymosin was found to significantly suppress the number of immunoglobulin synthesizing cells induced by PWM in cultures of human peripheral blood mononuclear cells. This observation, which is consistent with the known effects of thymosin on suppressor T cells, suggests that thymosin modulates B-cell function through an effect on suppressor T cells.

T cell inhibitor secreted by macrophages and endothelial cells

On stimulation with lipopolysaccharide (LPS), normal human macrophages (M phi) and endothelial cells (EC) produced factors which inhibited interleukin 2 (IL-2)-dependent lymphocyte proliferation and PHA plus interleukin 1 (IL-1)-dependent mouse thymocyte proliferation but not IL-1-dependent human fibroblast proliferation, suggesting that they were inhibitors of the IL-2 response. In addition, these factors inhibited the production of IL-2 by normal human peripheral blood mononuclear cells (PBMC). The factors also inhibited PBMC proliferation in response to PHA and concanavalin (Con A) but did not inhibit the proliferation of EC, U937 cells, or Epstein-Barr virus-transformed B cells. On Sephadex G200 gel filtration, the inhibitory factors from both M phi and EC were detected almost entirely in a 130- to 150-kDa fraction, but active material was also detected in a 15- to 20-kDa fraction. On isoelectric chromatofocusing of the 130- to 150-kDa fraction, inhibitory activity was associated with fractions eluted at three isoelectric points, pH 7.0, 5.4, and 4.8. The isoelectric fractions isolated from M phi and EC showed similar patterns of inhibition. When 130- to 150-kDa fractions from Sephadex G200 of the M phi and EC supernatants were treated with an antibody against a macrophage-derived suppressor factor produced by the human monocytic leukemia cell line THP-1, the activity of both fractions was neutralized. The above findings suggest that normal M phi and EC secrete an identical or closely related inhibitor of IL-2 synthesis and IL-2 response, and this inhibitor regulates these IL-2-related functions by a suppressive action on the T lymphocyte.