Cytokines in chronic inflammatory arthritis. IV. Granulocyte/macrophage colony-stimulating factor-mediated induction of class II MHC antigen on human monocytes: a possible role in rheumatoid arthritis.

Abstract

Granulocyte/macrophage CSF (GM-CSF) has recently been identified in rheumatoid arthritis (RA) synovial effusions. To study a potential role for GM-CSF and other cytokines on the induction of HLA-DR expression on monocytes and synovial macrophages, we analyzed the relative ability of recombinant human cytokines to induce the surface expression of class II MHC antigens on normal peripheral blood monocytes by FACS analysis. GM-CSF (800 U/ml) (mean fluorescence channel 2.54 .+-. 0.33 times the control, p < 0.001) and IFN-.gamma. (100 U/ml) (5.14 .+-. 0.60, p < 0.001) were the most potent inducers of HLA-DR. TNF-.alpha. and IL-4 also increased HLA-DR expression, although to a lesser degree [1.31 .+-. 0.06 (p < 0.02) and 1.20 .+-. 0.03 (p < 0.01), respectively]. IL-1 (40 U/ml), IL-2 (10 ng/ml), IL-3 (50 U/ml), IL-6 (100 U/ml), and CSF-1 (1,000 U/ml) did not affect surface HLA-DR density. GM-CSF also increased HLA-DR mRNA expression and surface HLA-DQ expression, but decreased CD14 (a monocyte/macrophage antigen) expression. The effect of GM-CSF on HLA-DR was not mediated by the generation of IFN-.gamma. in vitro because it was not blocked by anti-IFN-.gamma. mAb. GM-CSF was additive with IL-4 and low amounts (<3 U/ml) of IFN-.gamma. and synergistic with TNF-.alpha.. Because we have recently reported that supernatants of cultured RA synovial cells produce a non-IFN-.gamma. factor that induces HLA-DR on monocytes, we then attempted to neutralize this factor with specific anti-GM-CSF mAb. Four separate synovial tissue supernatants were studied, and the antibody neutralized the HLA-DR-inducing factor in each (p < 0.01).