Immunomodulatory assays to study structure-activity relationships of thalidomide.

Thalidomide, which has a long history of tragedy because of its ability to cause severe birth defects, is very effective in alleviating erythema nodosum leprosum in leprosy patients and aphthous ulcers in AIDS patients. The causes of these inflammatory diseases and the mechanism by which thalidomide diminishes them are unknown. It has been suggested that modulation of the immune response plays an important role. We found that thalidomide exerts immunomodulatory activity in three bioassays. It suppresses an IgM plaque forming cell response in mice injected with sheep erythrocytes: it inhibits TNF-alpha production by LPS stimulated human mononuclear cells: and it enhances IL-2 production by Con-A stimulated human mononuclear cells. We employed these bioassays to compare the activity of 15 analogs of thalidomide with thalidomide itself. Eight of the compounds were derivatives of the glutarimide moiety of thalidomide and the others were phthalimide or derivatives of the phthalimide moiety of thalidomide. N-hydroxyphthalimide, a simple derivative of phthalimide, was more effective than thalidomide and was also the most effective of the compounds assayed in suppressing the IgM plaque and TNF-alpha responses, but it did not enhance the IL-2 response, instead, it significantly suppressed it.

Effect of suppressor cells on antibody producing cells in mice infected with Mycobacterium leprae.

Swiss albino mice were transfused with suppressor cells obtained after in vivo stimulation of mice with Con A (NS group). Some of the animals were infected with Mycobacterium leprae (NSI-group). Half of these animals were treated with dapsone (NSIT group). Adequate normal (NC) and infected (NI) controls were included. A plaque assay was carried out at different time periods to elucidate the effect of suppressor cells on antibody producing cells. No significant difference was seen in the number of plaque forming cells (PFC) in infected and dapsone treated animals (NSIT) when these were compared with controls. However significant increase seen in the number of IgM plaque forming cells at 6 months in NI and NSI groups and IgG PFC in NI group could be due to the peak footpad infection during this period. The significant decrease in the number of IgG PFC in NS and NSIT group compared to NC at 0 month is probably due to the suppressor cell activity in these groups.

[Immunocorrective properties of new antileprotic preparations]. / Immunokorrigiruiushchie svoistva novykh protivoleproznykh preparatov.

Antimycobacterial and immunotropic characteristics of new antileprosy drugs, made in this country, have been studied and compared with those of dapsone. Animal experiments have demonstrated a high immunostimulating activity of the new drugs; this calls for clinical trials of these agents, for they may improve the therapy efficacy, help prevent the disease recurrences, and cut down the length of treatment for leprosy.