Monocytes In Multiple Sclerosis: Phenotype And Cytokine Profile
Kouwenhoven M, Teleshova N, Ozenci V, Press R, Link H
J NeuroImmunol 2001 Jan 1;112(1-2):197-205
Karolinska Institutet, Huddinge Univ Hospital, NeuroImmunology Unit, Division of Neurology, Stockholm, Sweden
Multiple Sclerosis (MS) is an inflammatory DeMyelinating disease characterized by Immune abnormalities in the Central Nervous System (CNS) as well as systemically.
Activated, blood-borne Monocytes are abundant in MS lesions, the properties of circulating Monocytes are incompletely known.
To delineate phenotype and levels of Cytokine secreting Monocytes in MS patients' blood, ELISPOT assays were used for detection and enumeration of Monocytes secreting the Cytokines IL-6, IL-12, TNF- and IL-10.
In parallel, the expression by Monocytes of co-stimulatory molecules (CD40, CD80, CD86), Major Histocompatibility Complex molecules (HLA-ABC, HLA-DR) and Fc receptors (CD16, CD64) was examined by flow cytometry.
Levels of blood Monocytes secreting IL-6 and IL-12 were higher in patients with untreated MS and Other Neurological Diseases (OND) compared to healthy controls.
While levels of Monocytes secreting TNF- and IL-10 did not differ between groups.
MS patients' blood Monocytes also displayed elevated mean fluorescence intensity for the co-stimulatory molecule CD86, and MS patients with longer disease duration (>10 years) and higher disease severity (EDSS >3) had higher percentages of CD80 expressing Monocytes.
Compared to patients with short duration or lower severity. In conclusion, Monocyte aberrations occur in MS and may change over the disease course.
Regulation Of Chemokine Receptor CCR5 And Production Of RANTES And MIP-1 By Interferon-ß
Zang YC, Halder JB, Samanta AK, Hong J, Rivera VM, Zhang JZ
J NeuroImmunol 2001 Jan 1;112(1-2):174-180
Baylor-Methodist Multiple Sclerosis Center, Multiple Sclerosis Research Laboratory, and Dept of Neurology
6501 Fannin Street, NB302, 77030, Houston, TX, USA
Trafficking of inflammatory T-Cells into the Brain is associated with interactions of certain Chemokines with their receptors, which plays an important role in the PathoGenesis of Multiple Sclerosis (MS).
We examined whether Interferon-beta (IFN-ß) had the ability to regulate the production of Chemokines and the expression of their receptors in T-Cells derived from patients with MS.
It was demonstrated for the first time that in vitro exposure of T-Cells to IFN-ß-1a selectively inhibited mRNA expression for RANTES and MIP-1 and their receptor CCR5.
T-Cell surface expression of CCR5 was significantly reduced in MS patients treated with IFN-ß, correlating with decreased T-Cell transmigration toward RANTES and MIP-1.
The study provides new evidence suggesting that IFN-ß treatment impairs Chemokine-induced T-Cell trafficking by reducing the production of RANTES and MIP-1 and the expression of their receptors CCR5.
ImmunoModulatory Effects Of Interferon-ß-1a In MS
Liu Z, Pelfrey CM, Cotleur A, Lee J, Rudick RA
J NeuroImmunol 2001 Jan 1;112(1-2):153-162
Cleveland Clinic Foundation, Dept of NeuroSciences, 44195, Cleveland, OH, USA
Several studies have established a role for Interferon-beta (IFN-ß) as a treatment for Relapsing/Remitting Multiple Sclerosis (MS). IFN-ß has been reported to decrease the relapse rate, relapse severity, progression of disability and development of new Brain lesions.
Its mechanisms of action, however, remain unclear. We hypothesize that ImmunoModulatory effects of IFN-ß may underlie its clinical efficacy.
We used IntraCellular Cytokine flow cytometry to analyze the effects of IFN-ß-1a on expression of the anti-inflammatory Cytokine, IL-10, and its effects on major co-stimulatory molecules in MS patients.
We found that Peripheral Blood MonoNuclear Cells (PBMC) produced more IL-10 following in vitro or in vivo treatment with IFN-ß-1a.
The primary cellular sources of IL-10 were Monocytes and CD4+ T-Lymphocytes.
IL-10 production in response to IFN-ß-1a was increased in unseparated PBMC compared to purified Lymphocyte cultures, indicating that interaction between Monocytes and Lymphocytes may influence IL-10 production in response to IFN-ß-1a.
Using flow cytometry, we monitored the ex vivo expression of two major co-stimulatory pairs-B7/CD28 and CD40/CD40L-before and after intramuscular IFN-ß-1a treatment of MS patients.
IFN-ß-1a lowered the expression of B7.1 on circulating B-Cells and increased B7.2 expression on Monocytes.
CD40 expression on B-Cells was down-regulated, but CD40 on Monocytes was up-regulated by IFN-ß-1a treatment.
These data suggest that co-stimulatory molecules are modulated by IFN-ß, providing a possible mechanism for its in vivo Immune Regulatory effects.