The novel arthritis-drug substance MCS-18 attenuates the antibody production in vivo

Kerek, F. and Szegli, G. and Cremer, Lidia and Lupu, Andreea-Roxana and Durbaca, Steliana and Calugaru, Ana and Herold, Aurora and Radu, D. L. (2008) The novel arthritis-drug substance MCS-18 attenuates the antibody production in vivo. Acta Microbiologica et Immunologica Hungarica, 55 (1). pp. 15-31. ISSN 1217-8950

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Abstract

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.Materials and 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.Discussion: 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 if MCS-18 may influence particularly the production of RA-specific auto-antibodies, too.

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