Histamine & Multiple Sclerosis

InterLeukin-6 (IL-6) is a ProInflammatory Cytokine whose synthesis is induced by a variety of stimuli including InterLeukin-1 (IL-1), Substance P (SP), and Histamine.

Because IL-6 has been implicated in the EtioPathology of different human diseases including Multiple Myeloma, Rheumatoid Arthritis, Multiple Sclerosis, Acquired ImmunoDeficiency Syndrome Dementia Complex, and Alzheimer's Disease, its inhibition may be of therapeutic interest.

A main demand on an effective inhibitor of IL-6 expression is that it inhibits IL-6 synthesis independently of the inducing stimulus.

We therefore used human Astrocytoma Cells to search for signal transduction cascades and transcription factors whose inhibition suppresses IL-6 synthesis after stimulation with three different inductors, IL-1ß, SP, and Histamine.

Whereas the antioxidant PyrroLidinedithioCarbamate was only able to inhibit IL-1-induced IL-6 expression, inhibition of protein kinase C prevented IL-6 expression induced by all three substances.

Promoter deletion analysis revealed that IL-1-induced IL-6 expression required the transcription factor Nuclear Factor-kB (NF-kB), whereas SP- and Histamine-induced IL-6 synthesis was essentially controlled by NF-IL-6.

These findings suggest that inhibition of protein kinase C or a combinatory inhibition of NF-IL-6 and NF-kB binding are strategies to effectively suppress IL-6 synthesis.

They therefore provide the basis for the development of AntiInflammatory drugs used to treat disorders in which IL-6 is Pathogenically involved.

Results indicate that during exacerbation, patients with Multiple Sclerosis showed marked T-Lymphopenia, decrease of Histamine-sensitive RFC while active RFC exhibited varied changes of their content; increase of the circulating Immune complexes, absence or low NIF level.

The effect of CorticoSteroid therapy on the NIF dynamics was evaluated and its level was found to be increased due to hormone treatment. Prednisolone furthers T-Cell ImmunoDeficiency and also reduces the intensity of AutoImmune reactions in Multiple Sclerosis.

NIF may be used as a prognostic criterion for the evaluation of completeness and duration of the remission. Prolonged functioning of NIF leads to suppression of the patient's Immune reactivity requiring ImmunoCorrection.

The authors investigated the amount of blood Histamine in 92 patients with Multiple Sclerosis, depending on the length of the disease and its clinical form. The biopsies of the Gastric Mucosa were studied in 32 patients.

It was established that the patients showed a high level of blood Histamine (disease length - under 5 years) and a low level (disease length - over 5 years). The histologic changes were pronounced in the Gastric Mucosa which is evaluated as a complication of Multiple Sclerosis.

A 36-year-old woman had, since the age of 24, numerous episodes of Visual Loss and Spinal Symptoms and Signs at various levels, and was diagnosed as Multiple Sclerosis (MS).

CSF Myelin-Basic-Protein was increased. Neurological and ElectroPhysiological investigations suggested the Peripheral Nerve involvement.

Sural Nerve biopsy performed about six years after the Onset, revealed severe loss of both Myelinated and UnMyelinated fibers. Subsequently, Histamine skin reaction was defective in the lower limbs.

Tests on SudoMotor and Pupillary functions indicated deficits of both Central and PostGanglionic (Ganglia) Sympathetic Systems.

Though we could not detect causative factors for the Peripheral Nerve lesions, our patient appears to be the first documented case of MS, associated with Axonal degeneration of the Peripheral Somatic and Autonomic Nervous Systems.

Using Oligodendrocytes from primary Brain cultures, as targets in an AntiBody-Dependent Cellular CytoToxicity (ADCC) assay, we have examined the effects of Insulin and Histamine on Killer Cells in Multiple Sclerosis (MS) and Other Neurological Disease (OND) controls compared to normal healthy controls.

The effects were shown to be specific for Effectors by preincubation experiments. MS patients' ADCC to primary Oligodendrocytes was depressed, but could be boosted to normal control levels by Histamine binding to the H1 Receptor.

Significant elevation of MS ADCC by Cimetidine alone suggested that endogenous Histamine production and H2 Receptor binding could be mediating a suppressive effect on MS ADCC to Oligodendrocytes.

In addition, MS ADCC could be boosted significantly by Insulin.

MS Killer Cells were more sensitive in vitro to the boosting effects of both Histamine and Insulin than either OND or normal controls, both in dose response and magnitude of the increased ADCC.

The CSF of twenty-six patients with Multiple Sclerosis (MS) and of twelve control persons was analyzed for Histamine and Histamine-N-MethylTransferase (HMT) activity.

Both in patients with Remitting and Progressive type of disease the Histamine level was about 60% higher than in the controls.

On the other hand in both groups of patients the HMT activity was significantly lower (32% and 40% respectively) than that of controls.