Thalidomide, which has a long history of tragedy because of its abilit
y to cause severe birth defects, is very effective in alleviating eryt
hema 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 suggeste
d that modulation of the immune response plays an important role. We f
ound that thalidomide exerts immunomodulatory activity in three bioass
ays. It suppresses an IgM plaque forming cell response in mice injecte
d with sheep erythrocytes; it inhibits TNF-alpha production by LPS sti
mulated human mononuclear cells; and it enhances IL-2 production by Co
n-A stimulated human mononuclear cells. We employed these bioassays to
compare the activity of 15 analogs of thalidomide with thalidomide it
self. Eight of the compounds were derivatives of the glutarimide moiet
y of thalidomide and the others were phthalimide or derivatives of the
phthalimide moiety of thalidomide. N-hydroxyphthalimide, a simple der
ivative of phthalimide, was more effective than thalidomide and was al
so the most effective of the compounds assayed in suppressing the IgM
plaque and TNF-cr responses, but it did not enhance the IL-2 response,
instead, it significantly suppressed it.