Emerging Immune Modulators

The phase III trials for currently approved MS immunotherapies followed the use of the therapy for 20 months or less. Long term efficacy and compliance can be an important factor since historic data show that people with MS lived on average 35 years following diagnosis even before current therapies (Smith and McDonald, 1999). Usually MS only decreases life expectancy by 2-3 years. However, prior to the advent of current therapies, 50% of those with MS needed assistance (a cane to walk over one half block) 15 years after diagnosis (Weinshenker et al, 1989). 

Eour of the five current immunomodulatory therapies are only approved for RR-MS and have not shown effectiveness in non-inflammatory SP-MS or more aggressive forms of the 

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Franco R, Pacheco R, Lluis C, Ahern GP, O Connell PJ.The emergence of neurotransmitters as immune modulators. Trends Immunol 2007 28(9) 400-407. 

Probiotics are live microorganisms that improve the health status of the host, and exert their effects primarily in the intestinal tract. A broad range of applications of probiotic cultures has emerged, and the application of probiotic cultures is restricted only by the ability of the cultures to survive in the different food types. Probiotic bacteria in the genera Lactobacillus and Bifidobacterium are most commonly used. The most important and well-documented health benefits of these genera are their effects on lactose digestion, intestinal microbial balance and dysfunction, immune modulation, hypersensitivity, carcinogenesis, and blood cholesterol levels. 

Since the identification of PAF in the early 1970 s, the autacoid has steadily emerged as a crucial mediator of diverse pathologies. Indeed, PAF is a potent mediator of anaphylaxis and inflammation and is also implicated in shock, graft rejection, renal disease, ovoimplantation and certain disorders of the central nervous system (CNS) [36,44]. There is also accumulating evidence that PAF is capable of modulating the immune response [45, 46]. 

Despite the fact that ulcerative colitis does not appear to have a Tul-type immune response mediated through TNF-a, some studies have shown a beneficial effect of TNF-a modulation in this disorder as well. Clearly, this area of IBD therapy is evolving rapidly as new drugs emerge and clinical experience increases. 

NK cells are important constituents of the primary natural immune system. NK cell function is modulated by the surface expression of MHC molecules. Unlike T cells, NK cells form a first line of defense and kill target cells without prior sensitization. In addition, stimulatory and inhibitory receptors signal and control NK cell function. Therefore, it is plausible that herpesviruses also address this aspect of natural immunity. The status of this emerging field of research is presented in two reviews. An even more recent addition to the field is the recognition of the importance of chemokines, cytokines and their receptors. As expected from a virus which has co-speciated with the host, herpesviruses use this information and divert it to their advantage. For a virus it makes no difference whether the cell itself responds to virus infection, e.g. by apoptosis or any other type of internal cellular antiviral regulation, or whether the reaction is systemic and involves several specialized cells. It is therefore not surprising that viruses have also found principles to avoid induced cell death. 

The role of NK cells in the adaptive immune response is to produce cytokines that modulate emerging T and B cell responses and eliminate infected or abnormal host cells prior to T and B cell activation. 

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