Thymic hormones and interferons in the treatment of rheumatoid arthritis.
Interferon gamma (IFN-gamma) is known to increase the rate of biosynthesis and membrane density of Ia in cells that have normal basal expression of Ia such as Ia+-monocytes and thymic epithelium. IFN-gamma also induces de novo expression of Ia in other cell types such as Ia- macrophages, vascular endothelium, fibroblasts, a.o. Consequently, IFN-gamma enhances the activation of specific T-helper cells and the immunity that is dependent on T-helper cells. If the antigen is a viral product expressed on the membrane of an infected cell, IFN-gamma inducing an aberrant Ia expression, will produce a T-helper cell activation from which the host will benefit. If the antigen presented by the newly Ia+ cell is an autologous cell membrane molecule, one that is unique to a particular tissue and of which the host T-helper cells are not tolerant, IFN-gamma can trigger an autoimmune attack. Several recent reports have described a decreased level and activity of IFN-gamma in the rheumatoid joint environment, in vitro as well as in vivo. It is still unknown whether these findings are due to a defective production or to a physiological down regulation of IFN-gamma in rheumatoid arthritis (RA). Consequently it is not clear whether the pharmacologic administration of IFN-gamma to RA patients would reduce the disease activity or induce a disease exacerbation. Initially, short term assays were performed with daily subcutaneous injections of IFN-gamma (50 micrograms or 100 micrograms). As some encouraging results were obtained, two double-blind long-term studies were started.(ABSTRACT TRUNCATED AT 250 WORDS)
Veys
E M
EM
Department of Rheumatology, Ghent University Hospital, Belgium.
Mielants
H
H
Vergruggen
G
G
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use; D007372:Interferons / Q000627:therapeutic use*; D007596:Joints / Q000187:drug effects; D013951:Thymus Hormones / Q000627:therapeutic use*
D013951:Thymus Hormones; D007371:Interferon-gamma; D007372:Interferons