The novel arthritis-drug substance MCS-18 attenuates the antibody production in vivo.
Influence of the novel arthritis drug-substance MCS-18 on the antibody (Ab) production against tetanus toxoid (TT) and diphtheria toxoid (DT) antigens was tested in vivo. Possible involvement of MCS-18 in Toll-like receptor (TLR) signalling pathway was further considered.


METHODS
Immunization of male CD1 mice was done with subcutaneous injection of TT emulsified in Freund's Complete (FCA) or Incomplete Adjuvant (FIA) and mixed diversly with MCS-18 and different test substances. To investigate the influence of TLR activation Pam3Cys and lipopolysaccharide (LPS) emulsified in FIA were tested in combinations with MCS-18. Antibody production was analysed in vivo by tetanus- or diphtheria-toxin neutralization test.


RESULTS
Immunogenicity of TT was significantly enhanced if administered together with FCA or TLR agonists Pam3Cys or LPS emulsified in FIA. It was shown that MCS-18 attenuated strongly the production of anti-TT Ab if administered together with the Ab elicitor FCA or TLR agonists in various combinations. MCS-18 was also active via oral administration.


CONCLUSIONS
These findings suggest that MCS-18 could be a potent, non-toxic antagonist or a down-regulator of TLR signalling pathway. Investigations on further models are needed to establish ifMCS-18 may influence particularly the production of RA-specific auto-antibodies, too.
Kerek
F
F
Cantacuzino Institute for Microbiology and Immunology, Bucharest, Romania. kerek@donatur.de
Szegli
G
G
Cremer
Lidia
L
Lupu
Andreea-Roxana
AR
Durbaca
Steliana
S
Calugaru
Ana
A
Herold
Aurora
A
Radu
D L
DL
D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation / Q000187:drug effects*; D004168:Diphtheria Toxoid / Q000276:immunology; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D011817:Rabbits; D013745:Tetanus Toxoid / Q000276:immunology; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors*
D000907:Antibodies, Bacterial; D004168:Diphtheria Toxoid; D007155:Immunologic Factors; D013745:Tetanus Toxoid; D051193:Toll-Like Receptors