IFN-beta reduces the number and severity of exacerbations of multiple sclerosis (MS), presumably by modifying immune regulation. We used semiquantitative polymerase chain reaction (RT-PCR) to measure mRNA levels for cytokines before and after IFN beta-1b therapy. mRNA was extracted from mononuclear cells of nine healthy controls and 31 patients with MS. Before therapy, IL-10 and leukemia inhibitory factor (LIF) mRNA levels were elevated in stable MS compared to active MS. Twenty four hours after IFN beta-1b treatment, mRNA levels for IL-1, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-gamma, TNF-alpha and LIF had not changed. At 1 week, TNF-alpha mRNA increased and IL-10 and LIF mRNA rose in 75% of patients. IL-2, IL-4, IL-12, IL-13 and IFN-gamma did not change. At 3 months, cytokine mRNA returned to baseline levels. mRNA for the IFN-induced antiviral enzyme, 2,5-OAS, rose by 24 h, peaked at 1 week, and remained elevated thereafter. Serum triglycerides and liver enzymes rose after therapy. Increased SGPT at 3 months correlated with TNF-alpha mRNA levels, suggesting that cytokines may cause some side effects of IFN beta-1b. Baseline cytokine mRNA levels reflect disease activity, but the therapeutic effect of IFN beta-1 b does not appear to be explained by changes in cytokine mRNA levels.

Monocytes, macrophages, and microglia have a central role in the CNS inflammation of MS. Monocytes are important in the earliest events in MS. Peripheral blood monocytes secrete prostaglandins before MS attacks. During clinical activity monocyte activation markers increase and IL-1 and TNF-alpha levels are elevated. Other monocyte products such as IL-10 reduce inflammation. IL-10 mRNA in MNC is increased during stable disease. Manipulation of monokine secretion and expression of monocyte surface proteins are reasonable approaches for immune therapy of MS.