Waubant E, Gee L, Miller K, Stabler G, Goodkin D
J Interferon Cytokine Res 2001 Mar;21(3):181-5
UCSF/Mt. Zion Multiple Sclerosis Center, San Francisco, CA 94115
PMID# 11331041; UI# 21229851
Serum levels of Matrix MetalloProtease-9 (MMP-9) and Tissue Inhibitor of MMP-1 (TIMP-1) were measured monthly in 7 patients with Relapsing/Remitting Multiple Sclerosis (MS).
6 months before and 6 months during treatment with weekly intramuscular (i.m.) injections of Interferon-beta-1a (IFN-ß-1a) 30 #mgr;g.
Within patient median MMP-9 levels were unchanged on treatment. Within-patient median TIMP-1 levels were higher during months 1-6 (771.5 ng/ml) and during months 4, 5, and 6 of treatment (793 ng/ml).
Compared with 6 months pretreatment (414 ng/ml) (respectively, p = 0.10, p = 0.047; Wilcoxon signed-rank test). These preliminary data suggest that IFN-ß-1a therapy may increase TIMP-1 levels.
IFN-ß-1b Augments GlucoCorticoid-Induced Suppression Of Tumor Necrosis Factor-alpha Production By Increasing The Number Of GlucoCorticoid Receptors On A Human Monocytic Cell Line
Uitdehaag BM, Hoekstra K, Koper JW, Polman CH, Dijkstra CD
J Interferon Cytokine Res 2001 Mar;21(3):133-5
Free University, Dept of Neurology, Amsterdam, The Netherlands
PMID# 11331035; UI# 21229845
We studied the effect of recombinant Interferon-beta-1b (IFN-ß-1b) on the sensitivity to GlucoCorticoids (GC) and on the number of GC receptors (GCR) in the human Monocytic cell line THP-1.
We found that IFN-ß-1b augments the suppressive effect that Dexamethasone has on the stimulated production of Tumor Necrosis Factor-alpha (TNF-).
Most likely related to the increased number of GCR observed after exposure to IFN-ß-1b, this provides a possible clue to the mechanism of action of IFN-ß in Multiple Sclerosis.
Pericot I, Tintoré M, Grive E, Briev L, Rovira A, Montalban X
Med Clin (Barc) 2001 Feb 17;116(6):214-216
Unitat de NeuroImmunologia Clinica, Servei de Neurologia, Servei de Radiologia, Hospital Vall d'Hebron, Barcelona
Isolated Spinal Cord Syndrome might be due to a first episode of Multiple Sclerosis.
The aim of the study was to determine the clinical usefulness and paraclinical characteristics and of Spinal and Brain MR imaging predicting conversion to Clinically Definite Multiple Sclerosis (CDMS) in patients with an Isolated Spinal Cord Syndrome.
Patients And Methods
We have evaluate thirty-eight patients with Isolated Spinal Cord Syndrome. A clinical protocol, Lumbar Puncture, Evoked Potential and Brain-Spinal Cord MRI were performed.
Twenty two percent of the patients fulfilling Brain MRI Paty's Criteria (p < 0.01), 54.5% Fazekas (p = 0.007) and 80% of patients fulfilling Barkhof's Criteria (p = 0.009) presented CDMS.
The Spinal MR imaging from CDMS patients was always abnormal, showing Cervical and marginal location with a diameter < 2 cm.
Brain MRI is strongly predictive of the risk of developing CDMS and Spinal Cord MRI may increase the sensitivity to detect conversion to CDMS.
Autonomic Regulation Of NeuroImmunological Responses: Implications For Multiple Sclerosis
Frohman EM, Monson NL, Lovett-Racke AE, Racke MK
J Clin Immunol 2001 Mar;21(2):61-73
Univ of Texas Southwestern Medical Center at Dallas, Dept of Neurology, Dallas, Texas 75235, USA
PMID# 11332655; UI# 21230168
The expression of Neural regulatory molecules by Immune Cells that infiltrate the Nervous System upon injury may be a mechanism for cross regulation between the Nervous System and the Immune System.
Several lines of evidence implicate nerve growth factor signaling through its receptors as a potential source of communication between the two systems.
The expression of ß-Adrenergic Receptors and Sympathetic innervation of Lymphoid Organs represents another example of communication between the Immune and the Nervous System.
In this review, we discuss mechanisms of how factors in common between the Nervous System and the Immune System may result in regulatory circuits which are important in both healthy and diseased states.
These studies may have relevance for a number of inflammatory conditions in humans, including Multiple Sclerosis.
The NeuroImmunology Of Multiple Sclerosis: Possible Roles Of T And B-Lymphocytes In ImmunoPathogenesis
O'Connor KC, Bar-Or A, Hafler DA
J Clin Immunol 2001 Mar;21(2):81-92
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Laboratory of Molecular Immunology, Boston, Massachusetts 02115, USA
PMID# 11332657; UI# 21230170
Multiple Sclerosis (MS) is an inflammatory disease of the Central Nervous System White Matter. The association of the disease with MHC Genes, the inflammatory White Matter infiltrates, similarities with animal models.
And the observation that MS can be treated with ImmunoModulatory and ImmunoSuppressive therapies support the hypothesis that AutoImmunity plays a major role in the disease pathology.
Evidence supports activated CD4+ Myelin-reactive T-Cells as major mediators of the disease. In addition, a renewed interest in the possible contribution of B-Cells to MS ImmunoPathology has been sparked by nonhuman primate and MS pathological studies.
This review focuses on the ImmunoPathology of MS, outlining the hypothetical steps of Tolerance breakdown and the molecules that play a role in the migration of AutoReactive cells to the CNS.
Particular focus is given to AutoReactive T-Cells and Cytokines as well as B-Cells and AutoAntibodies and their role in CNS PathoGenesis in MS.
Regulation By IFN-ß Of Inducible Nitric Oxide Synthase And InterLeukin-12/p40 In Murine Macrophages Cultured In The Presence Of Chlamydia Pneumoniae Antigens
Yao SY, Ljunggren-Rose A, Stratton CW, Mitchell WM, Sriram S
J Interferon Cytokine Res 2001 Mar;21(3):137-46
Vanderbilt Univ, School of Medicine, Dept of Neurology, Nashville, TN 37212
PMID# 11331036; UI# 21229846
Chlamydia Pneumoniae has been demonstrated in the CerebroSpinal Fluid (CSF) of patients with Multiple Sclerosis (MS). Interferon-beta (IFN-ß) has favorable effects on the clinical course of MS.
We investigated whether the beneficial effects of IFN-ß in MS may involve its role in regulating Nitric Oxide (NO) and InterLeukin-12 (IL-12) in Macrophages, as these Immune modulators form part of the Innate Immune response to IntraCellular pathogens, such as C. Pneumoniae.
Murine Macrophages in cultures exposed to elementary body antigens or recombinant Major Outer Membrane Protein (rMOMP) of C. Pneumoniae demonstrate a significant increase in NO as well as production of IL-12/p40 in culture supernatants compared with basal levels.
Addition of murine IFN-ß increased NO activity in murine Macrophages cultured with Chlamydial antigens. Addition of Neutralizing Anti-IFN-ß AntiBody prevented the NO increase.
In contrast to its effect on inducible NO Synthase (iNOS), IFN-ß reduced induction of IL-12/p40 following culture with either elementary body antigens or rMOMP. Inhibition was reversed with Anti-IFN-ß AntiBody.
If C. Pneumoniae infection is responsible for the inflammatory response in the PathoGenesis of MS, the beneficial effects of IFN-ß in MS may be due to its enhancing IntraCellular NO activity while inhibiting secretion of the proinflammatory Cytokine, IL-12.