Drop in relapse rate of MS by combination therapy of three different phosphodiesterase inhibitors

Abstract

Phosphodiesterase inhibitors (PDEIs), when used in combination, synergistically suppress TNFa production by various cells and also suppress experimental demyelination at very low concentrations. We conducted a pilot study to determine whether the combination of three PDEIs suppresses the relapse of MS at the usual therapeutic doses. Of the 12 relapsing remitting MS, the mean relapse rate/year dropped remarkably (from 3.08+3.32 to 0.92+1.86) after PDEI treatment. Seven out of 12 (58.3%) were relapse-free in the follow up period (499+142 days). The combination of three PDEIs can be safe and useful strategy for the future treatment of MS.

Keywords

multiple sclerosis cytokine TNFa relapse phosphodiesterase inhibitor

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References

Selmaj KW , Raine CS , Canella B , Brosnan CF. (1991) Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions . J Clin Invest 87: 949-953 .

Selmaj KW , Raine CS , Gross AH. (1991) Anti-tumor necrosis factor therapy abrogates autoimmune demyeli-nation . Ann Neurol 30: 697-700 .

Strieter RM et al. (1988) Cellular and molecular regulation of tumor necrosis factor-alpha production by pentoxifylline . Biochem Biophys Res Commun 155: 1230-1236 .

Suzumura A , Sawada M. (1999) Effects of vesnarinone on activation of murine microglia . Life Science 64: 1197-1203 .

Yoshikawa M , Suzumura A , Tamaru T , Takayanagi T. (1999) Effects of phosphodiesterase inhibitors on micro-glia . Multiple Sclerosis 5: 126-133 .

Suzumura A , Ito A , Yoshikawa M , Sawada M. (1999) Ibudilast suppresses TNFa production by glial cells functioning mainly as type III phosphodiesterase inhibitor in the CNS . Brain Res, 837: 203-212 .

Sommer N et al. (1995) The antidepressant rolipram suppresses cytokine production and prevents autoimmune encephalomyelitis . Nat Med 1: 244-248 .

Tamaru T , Suzumura A , Takayanagi T. (1998) Inhibitory effects of phosphodiesterase inhibitors on experimental autoimmune encephalomyelitis . Neuroimmunol 6: 154-155 .

Lacor M et al. (1994) cAMP upregulates IL-4 and IL-5 production from activated CD4+ T cells while decreasing IL-2 release and NF-AT induction . Int Immunol 6: 1333-1343 .

10.

Weber F et al. (1998) Synergistic immunomodulatory effects of interferon-b1b and the phosphodiesterase inhibitor pentoxifylline in patients with relapsingremitting multiple sclerosis . Ann Neurol 44: 27-34 .