Effects of antirheumatic drugs on sponge-induced granulation tissue, rheumatoid synovial tissue, matrix-free tendon cells and fibroblast plasma membranes in vitro.

Slices of sponge-induced, mature granulation tissue were incubated in the presence of antirheumatic drugs (sodium acetylsalicylate, indomethacin and phenylbutazone at concentrations of 10^?7–10^?2M) and labelled precursors of nucleic acids, proteins and acid mucopolysaccharides. Analogous experiments were made with sliced human synovial tissue from rheumatoid patients and with matrix-free embryonic chick tendon cells. The synthetic functions were suppressed by 10^?4–10^?3M indomethacin and phenylbutazone but only by 10^?2m acetylsalicylic acid. At low concentrations (10^?5–10^?6M) there was an increase in the radioactivity in proteins during the early period of the incubation but this was reversed later. Indomethacin and phenylbutazone affected the production of collagen at two points: (i) the synthesis of the peptide chain and. more notably, (ii) the secretion of collagen to the extracellular space. Indomethacin affected the final content of cellular collagen only slightly. Preliminary experiments on the effect of indomethacin on the activities of enzymes in plasma membranes prepared from granulation tissue showed some effect on leucyl-β-naphthylamidase and Na⁺, K⁺ -activated Mg²⁺- adenosine triphosphatase. The use of such systems for the screening of new connective tissue-active drugs is discussed. The secretion of collagen from matrix-free embryonic tendon cells is the most sensitive target for indomethacin in vitro.