What causes the alphaBcrystallin to manifest itself to begin with? Since MS is relapsing/remitting, then are we assuming the process begins somehow with alphaBcrystallin presenting itself and then the immune system attacking it? Why would it suddenly present itself? It is a protein that develops in response to nerve injuries. So it seems to me that something has happened even earlier than alphaBcrystallin to cause alphaBcrystallin to present itself at all, since it's a healing substance. Why does the body attack it then? And why does adding more alphaBcrystallin stop the attack and even reverse the damage?

This reminds me again of the vast unknown process involved with an immune response where certain things or levels of things trigger other things that trigger still other processes. So trying to play around with it to try to prevent the inflammatory process and yet not hinder the anti-inflammatory process is a very complex and complicated balancing act.

If this works, great. But it still doesn't answer the question of what is making the alphaBcrystallin manifest to begin with. Without knowing that, IF that is even a key initial episode, we will just be trying to mop up the damage and playing catch up.

My guess is that this is going to work similarly to adding more interferon into our bodies... but not much better.

J Immunol. 1996 Dec 15;157(12):5721-31.

The length of treatment determines whether IFN-beta prevents or aggravates experimental autoimmune encephalomyelitis in Lewis rats.

Ruuls SR, de Labie MC, Weber KS, Botman CA, Groenestein RJ, Dijkstra CD, Olsson T, van der Meide PH.
Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.

The mechanism of action underlying the beneficial effect of IFN-beta in multiple sclerosis (MS) is not understood. To date, little information is available on the effects of IFN-beta in experimental autoimmune encephalomyelitis (EAE), the animal correlate of the human disease MS.

Therefore, we investigated the effects of recombinant rat IFN-beta (rrIFN-beta) on EAE in Lewis rats with emphasis on a treatment regimen during the paralytic phase of the disease.

The results indicated that rrIFN-beta dose-dependently inhibited disease activity with complete prevention at a s.c. dose of 300,000 U/day, provided that treatment was continued for 3 wk. Discontinuation of treatment on day 17 postimmunization resulted in a protracted and relapsing disease course with strongly enhanced clinical severity. Detailed immunohistology of central nervous system (CNS) tissue of protected animals revealed an almost complete absence of CNS lesions and a >90% reduction in the number of infiltrating leukocytes. Accordingly, isolation of mononuclear cells from spinal cord tissue of successfully treated EAE rats revealed a reduction of approximately 95% in the number of cells that produce IFN-gamma in response to the encephalitogenic peptide MBP63-88. Furthermore, rrIFN-beta significantly enhanced serum corticosterone levels, which showed an inverse relationship with disease activity. We show that rrIFN-beta can have both beneficial and detrimental effects on disease activity dependent on the timing and the duration of treatment. Beneficial effects on EAE are associated with inhibition of the extravasation of blood-derived mononuclear cells in the CNS.

PMID: 8955226 [PubMed - indexed for MEDLINE]