Effects of bile salts and aliphatic ionic surfactants on human lymphocyte proliferation.
BACKGROUND
The molecular mechanisms involved in the immunosuppressive properties of bile salts are partly unknown.


METHODS
The aim of the study was to compare the effects of bile salts to those of various compounds with a steroid structure, or straight-chain hydrocarbons of different lengths and polar groups in the human mixed lymphocyte reaction.


RESULTS
We showed a significant correlation between the effects of bile salts 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 production without any effect on IL2 R expression. Fusidate, a negatively charged steroid, with physical properties comparable to those of deoxycholate, had similar effects. Cetyltrimethylammonium bromide (CTAB), which exhibited a very 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.


CONCLUSIONS
Amphiphilic negatively charged molecules inhibit T-cell proliferation to an extent that is dependent upon their hydrophobicity. These results may be explained, at least in part, by a modification in the cell membrane lipid bilayer structure.
Podevin
P
P
Unité d'Hépatologie, Hôpital Saint-Antoine, Paris, France. philippe.podevin@sat.ap-hop-paris.fr
Correia
L
L
Montet
J C
JC
Conti
F
F
Chéreau
C
C
Calmus
Y
Y
Poupon
R
R
D001647:Bile Acids and Salts / Q000494:pharmacology*; D002478:Cells, Cultured; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000494:pharmacology; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology*; D005765:Gastrointestinal Agents / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D007477:Ions / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013501:Surface-Active Agents / Q000494:pharmacology*
D001647:Bile Acids and Salts; D002593:Cetrimonium Compounds; D005227:Fatty Acids; D005765:Gastrointestinal Agents; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007477:Ions; D015375:Receptors, Interleukin-2; D013501:Surface-Active Agents; D002635:Chenodeoxycholic Acid; D000077286:Cetrimonium