IFNbeta-1a treatment and reestablishment of TH1 regulation in MS patients: dose effects.

We evaluated relationships between clinical and pharmacological parameters and the TH1/TH2/TH3 cytokine network in relapsing-remitting Multiple Sclerosis patients treated with differing doses of IFNbeta-1a. Our results show that low doses are ineffective but that high doses restore TH1 regulation of the maturation and activation of monocytes, T cells, immature-Dendritic Cells (IDCs), DCs and T regulatory cells (Trs) for central and peripheral self-tolerance. Interaction between IL10, IL12p70 and IL6 production appears to play an important role in the control of the maturation and activation states of DCs and Trs and is at the basis of the benefit of high doses. Our results also indicate that the physiological mechanisms involved in aging help immunological re-establishment in IFNbeta-1a treated patients. Finally, it would appear that the failure of IFNbeta-1a therapy to resolve multiple sclerosis completely is due to the suppression of IL12p70 mechanisms ( responsible for the physiological deletion of self-reactive cells) in activation conditions, probably by IFNbeta-1a itself.