THE PHOSPHODIESTERASE TV INHIBITOR ROLIPRAM IN-VITRO REDUCES THE NUMBERS OF MBP-REACTIVE IFN-GAMMA AND TNF-ALPHA MESSENGER-RNA EXPRESSING BLOOD MONONUCLEAR-CELLS IN PATIENTS WITH MULTIPLE-SCLEROSIS

The inflammatory nature of multiple sclerosis (MS) implicates the part icipation of cytokines as immune response mediators. Targeting the cyt okine balance by downregulating proinflammatory cytokines and/or upreg ulating immunosuppressive cytokines could benefit patients with MS. Th is article reports on the in vitro effects of the phosphodiesterase IV inhibitor Rolipram on the production of pro- and anti-inflammatory cy tokines in MS and, for reference, in myasthenia gravis (MG). Blood mon onuclear cells (MNC) were cultured in the presence of the organ-specif ic autoantigens myelin basic protein (MBP) or acetylcholine receptor ( AChR), and in the absence of antigens, with and without Rolipram. In s itu hybridization with synthetic oligonucleotide probes was used to de tect and enumerate blood MNC expressing IFN-gamma, TNF-alpha, LT, TGF- beta, IL-4, and IL-10 mRNA. Numbers of MNC-secreting IFN-gamma and IL- 4 in blood blood were examined by ELISPOT assays. Rolipram reduced the numbers of MBP-reactive IFN-gamma- and TNF-alpha mRNA-expressing bloo d MNC in MS, and numbers of AChR-reactive IFN-gamma-, TNF-alpha-, and LT mRNA-positive cells in MG. In contrast, expression of the Th2 cell related IL-4 and the anti-inflammatory IL-10, and TGF-beta was not aff ected. These data support a role for Rolipram in the treatment of dise ases such as MS.