Effect of high-dose steroid therapy on T-cell subpopulations. A longitudinal study in MS patients.

Lymphocyte subpopulations, T cell activation antigens, and serum levels of interleukin 2 (IL-2) and soluble IL-2 receptor (sIL2R), were studied in relapsing-remitting MS (RR-MS) patients before and after high-dose steroid therapy. Prior to therapy, a minority of patients showed increased HLA-DR antigen expression, and an increased number of CD16+ and CD19+ cells. Steroid treatment induced a significant increase in HLA-DR and CD19 expression, a significant reduction in CD16+, CD57+, and CD8+ CD57+ cells, and a slight, non-significant, decrease in IL-2 and sIL-2R levels and CD25 expression on CD4+ T lymphocytes.

On the role of interleukin-2 (IL-2) in multiple sclerosis (MS). IL-2-mediated endothelial cell activation.

Increased serum levels of IL-2 and sIL-2R can be demonstrated in patients with active MS, a finding that strongly supports the hypothesis of a systemic T cell activation in such patients. However, IL-2 may play a crucial role in MS immunopathology by activating endothelial cells, as suggested by the vascular leak syndrome complicating hrIL-2 therapy. Early BBB impairment and focal perivascular edema that characterize MS lesions may be the effect of an IL-2-induced cytokine cascade.

Effect of parenteral administration of GM1 on cytokines and anti-ganglioside antibody patterns. Preliminary report in normal human individuals.

To assess the effects of monosialoganglioside GM1 on some immunological parameters, 12 healthy men were treated with 100 mg GM1 i.m. daily for 15 days. Before and after treatment, the following were studied: (1) serum levels of antibodies against GM1, asialo-GM1 (aGM1), GM2 and GD1b; (2) serum levels of interleukin (IL)-1 beta, IL-2, soluble IL-2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma); (3) IL-1 beta and TNF-alpha production by peripheral blood monocytes (PBMO). Anti-ganglioside antibody and cytokine serum levels were not affected by exogenous GM1 administration with the exception of a transient increase in anti-GM1 antibody titer observed in one subject. In addition, no inhibition of IL-1 beta and TNF-alpha production by PBMO was observed. These preliminary data do not support a potential immunogenic or immunomodulatory function for in vivo administered GM1.

Immunological markers in the cerebrospinal fluid of HIV-1-infected children.

Several immunological abnormalities were detected in the cerebrospinal fluid (CSF) of human immunodeficiency virus type 1 (HIV-1)-infected children. Intrathecal synthesis of immunoglobulins, free light chains (FLC), IL-1 beta, IL-6, and M-CSF were demonstrated both in asymptomatic children and children with subacute encephalopathy. Our findings further support the hypothesis that an immunopathological subclinical process within the central nervous system (CNS) may be an early manifestation of acquired immunodeficiency syndrome (AIDS). Cytokine detection in the CSF may represent a useful diagnostic tool in evaluating the outcome of HIV-1-infected patients.

A longitudinal study on IL-2, sIL-2R, IL-4 and IFN-gamma in multiple sclerosis CSF and serum.

The cerebrospinal fluid (CSF) and serum levels of interleukin-2 (IL-2), soluble IL-2 receptor (sIL-2R), interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) were longitudinally investigated in 20 multiple sclerosis (MS) patients. There were 80 paired CSF and serum samples (range 2-8 per patient) covering a 1-5 year (mean 2.5 year) period. Increased levels of IL-2 and sIL-2R were found in 56 and 71%, respectively, of MS sera. In all patients, one or several sera (totally 89%) exhibited values above the normal range for either one of the components or both. The occurrence of IL-2 or sIL-2R positive CSF specimens was much lower, 15 and 9%, respectively. Only 3 MS sera (from one patient) had clearly detectable IL-4 and no CSF samples were definitely positive. IFN-gamma was undetectable in all serum and CSF specimens. No correlations were found between the immunological parameters and the clinical disease activity. The cytokine patterns in MS give strong support for the presence of a systemic T-cell activation. Furthermore, the data argue for a predominant activation of an IL-2- and sIL-2R-producing but not IL-4-producing T-helper (Th) lymphocyte subpopulation, Th1/CD4 + CD45R + cells.

Macrophage-colony stimulating factor (M-CSF) in the cerebrospinal fluid.

In a series of 145 cases with neurological diseases, macrophage-colony stimulating factor (M-CSF) was detected in cerebrospinal fluid of patients with brain tumors, bacterial meningitis, and less frequently, AIDS-dementia complex. Granulocyte-colony stimulating factor (G-CSF) was found only in patients with bacterial meningitis; granulocyte-macrophage (GM)-CSF was never detected. These findings suggest that M-CSF may play an important intrathecal immunoregulatory role in neoplastic and infectious diseases of the central nervous system.

Transferrin receptors in rat central nervous system. An immunocytochemical study.

Using an immunocytochemical method we demonstrated the presence of TfR on adult rat neurons, particularly in the cerebral cortex and brain stem. The monoclonal antibody (mab) against rat TfR (clone OX 26) stained neurons of all cortical layers and in the brain stem where the reaction was most evident. Purkinje cells in the cerebellum and scattered neurons in the gray matter of the cervical spinal cord were weakly stained. Choroid plexus cells also reacted with the mab against TfR whereas oligodendrocytes in the cerebral white matter were faintly outlined by the mab. The presence of TfR on endothelial cells of brain capillaries was here confirmed.

Free light chains of immunoglobulins in the cerebrospinal fluid of human immunodeficiency virus type 1-infected patients.

The presence of immunoglobulin (Ig) free light chains (FLC) was investigated in the cerebrospinal fluid (CSF) of human immunodeficiency virus type 1 (HIV-1)-infected patients. Intrathecal synthesis of FLC was demonstrated in 80% of the patients, even in the absence of oligoclonal Ig. The FLC patterns were characterized by restricted heterogeneity with regard to both isoelectric point and the molecular weight, and were mainly composed by dimers rather than monomers. A striking prevalence of lambda FLC was also observed. Local production of FLC can be taken as a marker of an ongoing immunopathological process within the central nervous system (CNS) in HIV-1-infected patients. A deregulation of Ig production by intrathecally activated B cells may be hypothesized.

Immune activation in multiple sclerosis: study of IL-2, sIL-2R, and gamma-IFN levels in serum and cerebrospinal fluid.

Serum and cerebrospinal fluid (CSF) levels of interleukin-2 (IL-2), soluble IL-2 receptor (sIL-2R), and gamma-interferon (gamma-IFN) were measured in multiple sclerosis (MS) patients, human immunodeficiency virus type 1 (HIV-1)-infected patients and normal controls (NC). Increased levels of both IL-2 and sIL-2R were found in MS serum. Moreover, 11 of 50 MS patients showed detectable levels of IL-2 in the CSF. HIV-1-infected patients had increased levels of sIL-2R in serum and, less frequently, in the CSF. gamma-IFN was never detected in serum and CSF of all the patients studied. These findings confirm preliminary reports, further stress a systemic T-cell activation in MS, and support the hypothesis that an immunologic disorder exists in such patients.

Tumor necrosis factor alpha (TNF alpha) and neurological diseases. Failure in detecting TNF alpha in the cerebrospinal fluid from patients with multiple sclerosis, AIDS dementia complex, and brain tumours.

The presence of tumor necrosis factor alpha (TNF alpha)/cachectin was investigated in 180 paired cerebrospinal fluid (CSF) and serum samples from patients with neurological diseases, and in five paired CSF and serum samples of Macaca cynomolgus monkeys with acute monophasic experimental autoimmune encephalomyelitis (AMEAE). TNF alpha was never detected in human CSF, even when an extensive demyelination was documented (active multiple sclerosis, acquired immunodeficiency syndrome (AIDS) dementia complex). Only one Macaca with AMEAE had detectable levels of TNF alpha in CSF but not in serum, suggesting an intrathecal synthesis of this cytokine in AMEAE.