Abstract
In vitro cultures of guinea-pig lymph node cells were stimulated to transform with phytchaemagglutinin (or antigen) and the incorporation of 3H-glucosamine, -leucine , 3H-uridine and 3H-thymidine measured. The inhibitory effect of established anti-inflammatory drugs and novel candidate compounds on some of these parameters and on cell viability was determined. FPL52806 affected the following measured parameters of stimulated cells, in decreasing order of sensitivity: -glucosamine incorporation at 40h ≈ [[3]H]-thymidine incorporation at 40h > 14C-leucine incorporation at 40 h. ≈ reduction in number of transformed cells > reduction in number of viable cells > 3H-uridine incorporation at 20h. > 3H-uridine incorporation at 1h. The effect of FPL52806 on 3H-thymidine and 14C-leucine incorporation were not due to interference with the binding of phytohaemagglutinin to the cells and were related to the length of time the cells had been exposed to the compound. FPL52806-treated cells were studied by scanning electron microscopy. The potencies of 6,8-di-alkyl chromones as inhibitors of 3H-thymidine and [[14]C]-leucine incorporations were shown to be mathematically related to the lipophilicities of the compounds. The extent to which these compounds bound to bovine serum was also related to the lipophilicity of the compounds. The order of decreasing potency of established anti-inflammatory drugs as inhibitors of 3H-thymidine incorporation was chloroquine, prednisolone, flufenamic acid, phenylbutazone, indomethacin, ibuprofen and sodium salicylate. This potency order is discussed with respect to the therapeutic potencies of the drugs in rheumatoid arthritis and to the activities of the drugs in other in vitro and in vivo test systems which may detect anti-inflammatory properties. The advantages of the stimulated lymph node cell system as anti-inflammatory screen are described. The biology of the lymphocyte and the evidence for the involvement of this cell in rheumatoid arthritis is described.