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Interferon-beta1b (IFN-beta1b) therapy is associated with a relatively high risk of developing thyroid disease. IFN-beta1a is regarded as less immunogenic than IFN-beta1b because of its structural homology to natural IFN-beta. We assessed the effect of 1 year of IFN-beta1a treatment on thyroid function and autoimmunity in 14 multiple sclerosis (MS) patients. The results were compared with those obtained in a series of 31 MS patients treated with IFN-beta1b. The prevalence of positive binding antibody (BAb) titer and neutralizing (NAb) anti-IFN antibody titer in the two groups was also assessed. The BAb and NAb positivity rate in IFN-beta1a-treated patients was significantly lower than in the group submitted to IFN-beta1b therapy (7% vs. 84% and 0% vs. 30%, respectively). Although the incidence of thyroid dysfunction was slightly higher in IFN-beta1b-treated patients than in those undergoing IFN-beta1a treatment (33% vs. 23%, respectively), it did not reach statistical significance. Thyroid disease was unrelated to the presence of positive serum BAb or NAb titer in both the group undergoing IFN-beta1a therapy and in that treated with IFN-beta1b. In both groups, thyroid disease developed mostly in women (71%) against a background of preexisting thyroiditis and a diffuse hypoechoic ultrasound thyroid pattern (80%). IFN-beta1a treatment was associated with a significantly lower prevalence of both BAb and NAb-positive titers than was IFN-beta1b. Conversely, thyroid disease was similar and unrelated to the presence of positive anti-IFN-beta antibody titer. Therefore, routine thyroid assessment may be advised during IFN-beta1a treatment, especially in patients with preexisting thyroiditis.

Multiple sclerosis (MS) is a T-cell-mediated autoimmune demyelinating disease of the central nervous system, associated with an altered cytokine network. We previously assayed peripheral blood T-lymphocyte binding for two prototypic cytokines, tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and found that T cells from MS patients had significantly more TNF-alpha and IL-6 receptors than those from healthy controls. In the present work, paralleling a previous one on T-cell TNF-alpha binding, we studied the effect of interferon (IFN)-beta-1b treatment on T-lymphocyte IL-6 binding in patients with relapsing-remitting MS. T cells from MS patients had significantly (P < 0.001) higher amounts of IL-6 receptors than those from controls [292 +/- 6 vs. 228 +/- 8 (mean +/- SEM) receptors per cell, respectively], whereas the ligand-receptor affinity values were similar in the two groups [26.2 +/- 0.7 and 25.7 +/- 0.4 (mean +/- SEM) pmoles/l, respectively]. After a 3-month IFN-beta-1b treatment, they showed a significant decrease in IL-6 binding [266 +/- 7 (mean +/- SEM) receptors per cell]. After 6 and 9 months, T-cell IL-6 B(max) values were even lower [258 +/- 8 and 251 +/- 8 (mean +/- SEM) receptors per cell]. Since an increased IL-6 binding might be linked to a lymphocyte activation, our data give further support for an enhanced immune response in patients with MS. Our data seem to demonstrate that the major effects of IFN-beta-1b treatment result in a decrease of T-cell activation.

Multiple sclerosis (MS) represents a T-cell-mediated autoimmune demyelinating disease of the central nervous system associated with altered immunoregulation. Interleukin (IL)-6 is a cytokine that has several effects on the neuroimmune system. Specific IL-6 receptors have been found in human lymphocytes and neuroglial cells. The aim of the present study was to assay IL-6 binding on peripheral blood T lymphocytes in MS patients. We found that T cells from MS patients had significantly more IL-6 receptors [Bmax: 279 +/- 7 vs. 246 +/- 8 (mean +/- SEM) receptors/cell, in patients and controls, respectively], whereas Kd values were similar to those of healthy subjects [26.8 +/- 0.7 vs. 25.4 +/- 0.6 (mean +/- SEM) pM, in patients and controls, respectively]. Significant (P < 0.05) differences in IL-6 binding values were observed between stable patients and those relapsing (272 +/- 9 vs. 300 +/- 12 (mean +/- SEM) receptors/cell, respectively). We found significantly (P < 0. 001) higher amounts of IL-6 receptors on CD4+ T cells from MS patients than on CD4+ lymphocytes from controls (434 +/- 11 vs. 363 +/- 9 (mean +/- SEM) receptors/cell, respectively); CD8+ T cells showed very few IL-6 receptors in both patients and controls. These data are discussed in terms of MS immune pathogenesis and pathophysiology, because T-cell activation seems to be linked to increased IL-6 binding. The upregulated IL-6 system might be involved in antibody-mediated demyelinating pathways, because IL-6 is well known to enhance humoral immune response.

Objective To investigate the effects of interferon beta treatment on T-cell interferon gamma binding (which is a possible marker for T-cell–dependent immune function) in patients with multiple sclerosis (MS). Design Assay interferon gamma binding on T lymphocytes from patients with stable relapsing-remitting MS before, 3 months after, and 6 months after initiating interferon beta-1b treatment. Setting The study was performed on ambulatory patients in a tertiary care center, where patients were diagnosed as having definite MS. Patients Eighteen patients with clinically definite, stable, relapsing-remitting MS (13 women and 5 men; mean age [± SD] 32.6 ± 7.1 years) were selected consecutively. Clinical status was defined according to the Kurtzke Expanded Disability Status Scale. All patients were treated with 8 × 10 6 IU interferon beta-1b subcutaneously every other day. Eighteen age- and sex-matched healthy subjects with no family history of neuropsychiatric disorders formed the control group. Results T lymphocytes from untreated patients with MS had significantly smaller amounts of interferon gamma receptors than those from control subjects (638 ± 7 [SE] vs 707 ± 11 [SE] receptors per cell). After 3 months of interferon beta-1b treatment, they showed a significant increase in interferon gamma binding (681 ± 9 [SE] receptors per cell). After 6 months, T-cell interferon gamma maximal receptor values were even higher (700 ± 7 [SE] receptors per cell), only slightly lower than those of control subjects. Conclusion Given that reduced interferon gamma binding might be related to lymphocyte activation, our data seem to demonstrate that the major effect of interferon beta-1b treatment is a decrease in T-cell activation.

To investigate the effects of interferon beta treatment on T-cell tumor necrosis factor alpha (TNF-alpha) binding (which is a possible marker for T-cell-dependent immune function) in patients with multiple sclerosis.The TNF-alpha binding on T lymphocytes from patients with stable relapsing-remitting multiple sclerosis was assayed before and 3 and 6 months after the start of treatment with interferon beta.The study was performed on ambulatory patients in a tertiary care center.Eighteen patients with clinically definite stable relapsing-remitting multiple sclerosis (13 women and 5 men; mean [+/-SD] age, 32.6+/-7.1 years) were selected consecutively. Clinical status was defined according to the Expanded Disability Status Scale. All patients were treated with 8 x 10(6) U of interferon beta-1b subcutaneously every other day. Eighteen age- and sex-matched healthy subjects, with no family history of neuropsychiatric disorders, served as controls.T lymphocytes from untreated patients with multiple sclerosis had significantly more TNF-alpha receptors than those from controls (mean+/-SE, 837+/-33 vs 135+/-5 receptors per cell). After 3 months of treatment with interferon beta-1b, they showed a significant decrease (P.001) in TNF-alpha binding (452+/-29 receptors per cell). After 6 months, T-cell TNF-alpha maximal receptor numbers were even lower (345+/-35 receptors per cell).Given that increased TNF-alpha binding might be linked to lymphocyte activation, our data demonstrate that a major effect of interferon beta-lb treatment is to decrease T-cell activation.

Rates of disease progression differ among patients with Alzheimer's disease, but little is known about prognostic predictors. The aim of the study was to assess whether sociodemographic factors, disease severity and duration, and vascular factors are prognostic predictors of cognitive decline in Alzheimer's disease progression. We conducted a longitudinal clinical study in a specialized clinical unit for the diagnosis and treatment of dementia in Rome, Italy. A total of 154 persons with mild to moderate Alzheimer's disease consecutively admitted to the dementia unit were included. All patients underwent extensive clinical examination by a physician at admittance and all follow-ups. We evaluated the time-dependent probability of a worsening in cognitive performance corresponding to a 5-point decrease in Mini-Mental State Examination (MMSE) score. Survival analysis was used to analyze risk of faster disease progression in relation to age, education, severity and duration of the disease, family history of dementia, hypertension, hypercholesterolemia, and type 2 diabetes. Younger and more educated persons were more likely to have faster Alzheimer's disease progression. Vascular factors such as hypertension and hypercholesterolemia were not found to be significantly associated with disease progression. However, patients with diabetes had a 65% reduced risk of fast cognitive decline compared to Alzheimer patients without diabetes. Sociodemographic factors and diabetes predict disease progression in Alzheimer's disease. Our findings suggest a slower disease progression in Alzheimer's patients with diabetes. If confirmed, this result will contribute new insights into Alzheimer's disease pathogenesis and lead to relevant suggestions for disease treatment.