Background The molecular mechanisms involved in the immunosuppressive prope
rties of bile salts are partly unknown.
Methods The aim of the study was to compare the effects of bile salts to th
ose of various compounds with a steroid structure, or straight-chain hydroc
arbons of different lengths and polar groups in the human mixed lymphocyte
reaction.
Results We showed a significant correlation between the effects of bile sal
ts and a low critical micellar concentration, a high surface activity index
, and the absence of conjugation. In addition to mixed lymphocyte reaction
(MLR) inhibition, chenodeoxycholate (CDC) inhibit ConA-induced IL2 producti
on without any effect on IL2 R expression. Fusidate, a negatively charged s
teroid, with physical properties comparable to those of deoxycholate, had s
imilar effects. Cetyltrimethylammonium bromide (CTAB), which exhibited a ve
ry low critical micellar concentration, inhibited mixed lymphocyte reaction
in an extent comparable to cyclosporin A. In contrast, aliphatic compounds
with critical micellar concentrations in the same range as bile salts but
with a lower molecular area had no effect.
Conclusion Amphiphilic negatively charged molecules inhibit T-cell prolifer
ation to an extent that is dependent upon their hydrophobicity. These resul
ts may be explained, at least in part, by a modification in the cell membra
ne lipid bilayer structure.