Time-course of interleukin-2 receptor expression in interferon beta-treated multiple sclerosis patients.

The time-course of CD25 (the 55-kD/alpha subunit of the interleukin-2 (IL-2) receptor) expression on CD4+ T lymphocytes, and serum levels of soluble IL-2 receptors (sIL-2R) and IL-2 were evaluated in relapsing-remitting multiple sclerosis (RRMS) patients treated with interferon beta-1b (IFNbeta1b). Peripheral blood samples were collected before therapy (T0), and 1 (T1), 2 (T2), 3 (T3), 6 (T4), and 12 (T5) months after therapy initiation. While at T1 and T2, half the patients showed an increased number of circulating CD4+ CD25+ lymphocytes and an up-regulation of CD25 expression, at T3 this T-cell subset was significantly reduced in all the patients. From T4 to T5, however, the progressive return to pretreatment values was observed. Serum sIL-2R levels were not significantly affected by IFNbeta1b at any time point. IL-2 was detected in only a few patients at T0, and never at T1 to T5. The transient up-regulation of CD25+ expression that occurred in about 50% of the patients may explain the unchanged relapse rate observed during the first 2 to 3 months after starting IFNbeta1b therapy. Our study demonstrates that IFNbeta1b down-regulates CD25 expression in vivo. This effect, however, was observed only after 3 months of therapy, and was followed by the return to pretreatment values after 6 to 12 months. Taken all together, our findings suggest that IFNbeta1b only transiently affects CD25 expression in vivo, and that this effect cannot account for the reported long-lasting beneficial action of IFNbeta1b on RRMS.

Cytokine pattern in the cerebrospinal fluid from patients with GBS and CIDP.

Macrophage-colony stimulating factor (M-CSF) and, less frequently, IL-1 beta and IL-6 were detected in the cerebrospinal fluid (SF) from Guillain-Barré syndrome (GBS) patients. IL-1 alpha, IL-2, IL-10, TNF alpha, and IFN gamma were not found. Detectable cytokine levels were not observed in chronic inflammatory demyelinating polyneuropathy (CIDP) SF nor in any of the sera studied. These findings suggest a prominent intrathecal activation of cells of the monocyte/macrophage lineage (Mø) in GBS, and further support the hypothesis of a crucial role for Mø in GBS immunopathology.

Cerebrovascular and neurological disorders associated with antiphospholipid antibodies in CSF and serum.

Paired serum and cerebrospinal fluid (CSF) samples from 70 patients with inflammatory and non-inflammatory neurological diseases, as well as 10 sera from patients with primary antiphospholipid syndrome (PAS), six of which presented with cerebrovascular ischemic syndromes, were studied for the presence of anticardiolipin antibodies (ACA) of the G and M classes. PAS sera and some selected paired CSF and serum specimens, were also analyzed for the presence of anti-phosphatidylserine (PS) and anti-phosphatidylethanolamine (PE) antibodies. High levels of IgG and IgM ACA were synthesized intrathecally only in patients with neurosyphilis. Patients with other infectious or inflammatory neurological diseases very rarely showed detectable levels of ACA in serum and/or CSF. ACA were found not only in patients with untreated PAS but also in the serum of 3/7 patients with migraine, thus confirming a relationship between ACA and vascular disorders. The search for PS and PE antibodies disclosed that in PAS patients the serum titers of these antibodies mirrored ACA IgG and IgM titers, while they were never found in the CSF.

Multiple sclerosis: IL-2 and sIL-2R levels in cerebrospinal fluid and serum. Review of literature and critical analysis of ELISA pitfalls.

The presence of interleukin-2 (IL-2) and soluble IL-2 receptors (sIL-2R) in the serum and cerebrospinal fluid (CSF) of patients suffering from multiple sclerosis (MS) has been extensively investigated. These studies, however, have produced conflicting results. The only significant finding concerns the frequent detection of increased sIL-2R levels in the serum in patients with relapsing-remitting MS (RRMS), especially after a short interval of time from the last relapse. Whether this finding can be used for clinical purposes requires further investigation. A standardization of the ELISA methods used to detect cytokines in biological fluids is urgently needed. Increased serum and/or CSF levels of IL-2 and sIL-2R strongly confirm a CD4+ Th1 activation.

Time-course analysis of CD25 and HLA-DR expression on lymphocytes in interferon-beta 1b-treated multiple sclerosis patients.

To identify immunological markers that could be used to monitor relapsing-remitting multiple sclerosis (RRMS) course/activity during interferon beta 1b (IFN beta 1b) therapy, we longitudinally studied HLA-DR and CD25 expression by T lymphocytes in 15 IFN beta 1b-treated RRMS patients. Peripheral blood T cell subsets were analysed before therapy (T0), and after 1 (T1), 2 (T2), 3 (T3), 6 (T4) and 12 (T5) months after therapy initiation. HLA-DR expression and the CD3+HLA-DR+ T cell number showed a peculiar trend in almost all (14/15) the patients: a significant decrease at T1 and T2 followed by a return to pre-treatment levels from T3 to T5. At T1 and T2, eight patients showed an up-regulation of CD25 on CD4, as well as an increase in the CD4+CD25+ cell number. However, a marked, significant reduction of this T cell subset was observed in all the patients at T3, followed by the progressive return to pre-treatment values from T4 to T5. All the patients developed anti-IFN beta 1b 'binding' antibodies within the first three months of therapy. Our findings demonstrate that: (1) the expression of HLA-DR and CD25 on T cells, as well as the number of circulating CD3+HLA-DR+ and CD4+CD25+ cells, are only transiently reduced in vivo in IFN beta 1b-treated RRMS patients, (2) the expression of HLA-DR and CD25 on T lymphocytes cannot be used to monitor MS course/activity during IFN beta 1b therapy, (3) the long-lasting beneficial effect of IFN beta 1b on RRMS reported in the literature cannot be explained by the down-regulation of MHC class II antigens and/or interleukin-2 receptor expression induced by this cytokine.