Reduction of monocyte-macrophage activation markers upon anti-CD4 treatment. Decreased levels of IL-1, IL-6, neopterin and soluble CD14 in patients with rheumatoid arthritis

Abstract

SUMMARY: Anti-CD4MoAbs have been successfully used in initial treatment trials of rheumatoid arthritis. One remarkable feature of this therapy was the early reduction of synovitis along with a decrease of the erythrocyte sedimentation rate (ESR) and the C-reactive protein (CRP). Since not only T helper celis. but also monocytes-maerophages bear the CD4 antigen, the question was raised whether the immediate elTects observed may have been in part due to an influence on the mononuclear phagocyte system. Inimediately after MoAb infusions, a significant reduction of the absolute peripheral blood monocyte count down to 30%(P < 0·001) was noted within the firsl hour of injection. In contrast to strikingly elevated levels of soluble CD4 after treatment which was indicative of T cell lysis, soluble CD14 levels did not rise, but rather decreased from previously elevated levels. Before treatment, aetivation of the monocyte-macrophage system had been signified by elevated serum levels of IL-1, IL-6. CRP and neopterin as well as a marked in vitro production of IL-1. tumour necrosis faetor-alpha (TNF-α)and IL-6. Subsequent anti-CD4 treatment resulted in a rapid and significant reduction of monocyte-derived circulating cytokines and mediators concordant with a reduced capacity to produce IL-1. TNF-α, and IL-6 in those paiients who demonstrated clinical benefits. Therefore, studies of monocyte aetivation markers may be useful in identifying subsequent responders to anti-CD4 therapy.