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GlucoCorticoids (Steroids)

  1. Immunological effects of oral high-dose MethylPrednisolone in acute Optic Neuritis and Multiple Sclerosis
    Eur J Neurol 2000 May;7(3):281-9

  2. Bulk Files
    Optic Neuritis Treatment Trials

  3. Bulk Files:

  4. Bulk Files
    Oral vs IV Steroid in Multiple Sclerosis

  5. Bulk Files
    MethylPrednisolone in Multiple Sclerosis

  6. CorticoSteroids effects on Neutrophil molecules
    Int J Clin Lab Res 28: 110-5 (1998)

  7. Adhesion molecules in the ImmunoPathoGenesis of MS
    Neurology 1997;49:1111-16

  8. Chronic Prednisone use causes Memory loss
    Neurology 1996;47:1396-1402

  9. MethylPrednisolone has limited duration effects on MRI changes
    NeuroRadiology 1994 Jul;36(5):382-7

  1. Effects of IV MethylPrednisolone on Brain atrophy in Relapsing/Remitting MS
    Neurology 2001 Oct 9;57(7):1239-47

  2. Effect of Steroids on Gd-enhancing lesions before and during Interferon-ß-1a treatment in Relapsing/Remitting Multiple Sclerosis
    Neurology 1998 Feb;50(2):403-6

  3. GlucoCorticoid can inhibit expression of TNF-alpha
    October 22, 1997





#1

Effects Of IV MethylPrednisolone On Brain Atrophy In Relapsing/Remitting MS

Zivadinov R, Rudick RA, De Masi R, Nasuelli D, Ukmar M, Pozzi-Mucelli RS, Grop A, Cazzato G, Zorzon M
Neurology 2001 Oct 9;57(7):1239-47
University of Trieste, Departments of Clinical Medicine and Neurology, Radiology, and Electrical, Electronics, and Computer Science, Italy
PMID# 11591843; UI# 21475996
Abstract

Background
IV MethylPrednisolone (IVMP) has been used to treat relapses in patients with Relapsing/Remitting (RR) MS, but its effect on disease progression is not known. Furthermore, there are no data on the impact of IVMP on T1 black holes or Whole-Brain Atrophy.

Objective
To determine the effect of IVMP on MRI measures of the destructive pathology in patients with RR-MS and secondarily to determine the effect of IVMP on disability progression in patients with RR-MS.

Methods
The authors conducted a randomized, controlled, single-blind, phase II clinical trial of IVMP in patients with RR-MS.

Eighty-eight patients with RR-MS with baseline Expanded Disability Status Scale (EDSS) scores of </=5.5 were randomly assigned to regular pulses of IVMP (1 g/day for 5 days with an oral Prednisone taper) or IVMP at the same dose schedule only for relapses (IVMP for relapses).

And followed without other disease-modifying drug therapy for 5 years. Pulsed IVMP was given every 4 months for 3 years and then every 6 months for the subsequent 2 years.

Patients had quantitative Cranial MRI scans at study entry and after 5 years and standardized clinical assessments every 4 to 6 months.

Results
Eighty-one of 88 patients completed the trial as planned, and treatment was well tolerated. Baseline demographic, clinical, and MRI measures were well matched in the two study arms.

Patients on the pulsed IVMP arm received more MP than patients on the control arm of the study (p < 0.0001).

Mean change in T1 Black Holes volume favored pulsed IVMP therapy (+1.3 vs +5.2 mL; p < 0.0001), as did mean change in Brain Parenchymal Volume (+2.6 vs -74.5 mL; p = 0.003).

There was no significant difference between treatment arms in the change in T2 volume or annual relapse rate during the study.

However, there was significantly more EDSS score worsening in the control group, receiving IVMP only for relapses.

There was a 32.2% reduction (p </= 0.0001) in the probability of sustained EDSS score worsening in the pulsed MP arm compared with the relapse treatment arm.

At the end of the study, EDSS was better in the pulsed MP group (1.7 vs 3.4; p < 0.0001). Prolonged treatment with pulsed IVMP was safe and well tolerated; only two patients dropped out for toxic side effects over 5 years.

Conclusions
In patients with RR-MS, treatment with pulses of IVMP slows development of T1 Black Holes, prevents or delays Whole-Brain Atrophy, and prevents or delays disability progression. A phase III study of IVMP pulses is warranted.



#2

Effect Of Steroids On Gd-Enhancing Lesions Before And During Interferon-ß-1a Treatment In Relapsing/Remitting Multiple Sclerosis

Gasperini C, Pozzilli C, Bastianello S, Koudriavtseva T, Galgani S, Millefiorini E, Paolillo A, Horsfield MA, Bozzao L, Fieschi C
Neurology 1998 Feb;50(2):403-6
Univ of Rome La Sapienza, Dept of Neurological Sciences, Italy
PMID# 9484362; UI# 98145356
Abstract

The aim of this study was to investigate whether a concomitant treatment with recombinant Interferon-ß-1a (rIFN-ß-1a) modifies the effect of Steroids on the Blood-Brain Barrier (BBB) in Relapsing/Remitting MS patients, as evaluated by enhanced MRI of the Brain.

We evaluated 19 patients with a clinical relapse treated only with IntraVenous MethylPrednisolone (IVMP; 1 g daily for 6 days), and 10 patients who experienced a clinical relapse and were treated with IVMP (1 g daily for 6 days) during an rIFN-ß-1a treatment period.

The number and volume of Contrast Enhancing Lesions were analyzed on four serial MR images obtained at monthly intervals (one scan before and three scans after IVMP treatment).

A significant reduction in the mean number and volume of enhancing lesions was seen in the first scan after IVMP treatment in all patients.

However, while persistently low enhancement was seen in the follow-up scans of patients treated with rIFN-ß-1a, a rebound effect (i.e., increase in the number and volume of Gadolinium-enhancing lesions) was observed in the other patients during the follow-up.

These data suggest that rIFN-ß-1a prolongs the beneficial effect of Steroids on the BBB.



#3

New Method To Halt Inflammation
In AutoImmune Diseases

    DALLAS - October 22, 1997


A Steroid produced in the Adrenal Glands can halt production of a molecule integral to Inflammatory and AutoImmune afflictions such as Rheumatoid Arthritis and Lupus, reported researchers at UT Southwestern Medical Center at Dallas.

The scientists described their finding that the Hormone GlucoCorticoid can inhibit expression of the Tumor Necrosis Factor-alpha (TNF-alpha) Gene in the November issue of the journal Molecular and Cellular Biology.

GlucoCorticoid blocks an enzyme - Jun N-terminal kinase (JNK)/Stress-Activated Protein Kinases (SAPK) - that is part of the signaling pathway controlling cell behavior.

"TNF has become a very interesting molecule because it plays such a central role in a variety of diseases, so anything affecting TNF production might potentially be a drug," said Dr. Thomas Geppert, UT Southwestern associate professor of Internal Medicine.

"Current approaches to block TNF production are expensive and require repeated injections, but if we could come up with a pill that blocks TNF production it would be a real breakthrough."

Previous research showed that GlucoCorticoids are among the most potent and clinically important ImmunoSuppressant drugs, but it was not known how they inhibit Inflammation.

This research suggests a mechanism for this effect. "GlucoCorticoids inhibit LipoPolySaccharide (LPS)-induced TNF production," Geppert said. "It looks like Steroids bar TNF production by blocking JNK activation.


That is interesting because Steroids play such an important role in the therapy of Inflammatory disorders. Although Steroids are frequently effective, they have Significant Toxicity.

It is hoped a lot of that ImmunoSuppressant effect of Steroids might be through their effects on TNF and much of its Toxicity might be mediated through other pathways."

Although GlucoCorticoids may decrease Inflammatory symptoms, because they regulate Carbohydrate and Protein Metabolism, Stimulate Glucose Production and Elevate Blood Pressure, they frequently cause:


"Understanding how GlucoCorticoids work biochemically will lead to better drugs that don't have these Side Effects," Geppert said. Geppert's research team will next attempt to understand the mechanism by which Steroids affect JNK activation.

"We need to understand the whole signaling pathway in order to identify events that are unique to TNF production. If these events are specific to TNF production, drugs that inhibit them will be less likely to affect other signaling pathways leading to side effects.

The development of drugs with the ability to block Inflammation as well as Steroids do; but without the side effects is the dream of most physicians who deal with Inflammatory Disorders like Arthritis, Asthma or Colitis."

Other researchers who participated in the study were Dr. Melanie Cobb, professor of Pharmacology and holder of the Jane and Bill Browning Jr. Chair in Medical Science, and Jennifer Swantek, research fellow in Internal Medicine.


This study was funded in part by the American Heart Association





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