There is some evidence to suggest that pregnant women with multiple sclerosis experience a diminished frequency and severity of relapse in the last trimester of pregnancy. This has prompted investigators to assess whether hormones such as progesterone are capable of inhibiting multiple sclerosis in animal models. Indeed this seems to be the case.
For example, Garay et al (Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis. Neuroimmunomodulation 2008;15(1):76-83) used the B6 mouse model of multiple sclerosis (immunized with peptide from myelin oligodendrocyte protein 40-54) to demonstrate that administration of progesterone before induction of pathology led to suppressed disease severity index, inhibition of demyelination and increased expression of the sodium-potassium-ATPase gene in motor neurons. Another study, (Correale et al. Steroid hormone regulation of cytokine secretion by proteolipid protein-specific CD4+ T cell clones isolated from multiple sclerosis patients and normal control subjects. 1998 Oct 1;161(7):3365-74) demonstrated that culture of T cells in progesterone upregulated ability to generate interleukin-4, a Th2 cytokine. This is shown in the figure below.
Now we on the one hand we know that hormones affect immunological cells, but do hormones such as progesterone alter the ability of stem cells to modulate immune responses? It appears that they do. Ivanova-Todorova et al published (HLA-G expression is up-regulated by progesterone in mesenchymal stem cells. Am J Reprod Immunol. 2009 Jul;62(1):25-33) that treatment of mesenchymal stem cells with progesterone increased expression of the immune modulatory protein HLA-G. This implies that ex vivo treatment of mesenchymal stem cells with progesterone may be useful in augmenting their ability to alter immune responses. Additionally, it would be interesting to see if in vivo synergy may be obtained by treating patients with hormones and concurrently administering stem cells.
The ability to augment therapeutic activity of mesenchymal stem cells is very appealing since these cells are already in Phase III clinical trials by the company Osiris Therapeutics for treatment of Graft Versus Host Disease. Once these cells are approved for marketing purposes (anticipated to be next year), then physicians will be able to use them on a more widespread basis and in many situations for off-label uses. This will cause a great interest in methods of augmenting their efficacy, including methods as mentioned above.