Multiple Sclerosis Society of Canada

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MS Society-funded fellow demonstrates the ability of the hormone prolactin, when combined with interferon-β, to reduce disease severity in animals with MS-like disease.

  • Canadian Study
  • MS Society Funded

Background

While we know that women living with multiple sclerosis (MS) often experience fewer relapses during mid to late pregnancy or while breastfeeding, we are not sure why this occurs. One possibility lies with the hormone prolactin. Necessary for milk production, prolactin is at its highest levels in women during the third trimester of pregnancy and while breastfeeding. MS Society-funded researcher Dr. Wee Yong and colleagues previous showed that in female mice, prolactin promotes oligodendrocyte and myelin production, leading to remyelination. However, prolactin can be pro-inflammatory, a serious concern if used to treat an autoimmune disease such as MS.

To determine how prolactin fares as a potential MS therapeutic, Dr. Wee Yong and his Calgary-based team, including MS Society-funded fellow Dr. Simon Zhornitsky, administered the hormone to female mice with an MS-like disease. Their study was recently published in the Journal of Neuroinflammation.

The Study

Researchers induced an MS-like disease, dubbed experimental autoimmune encephalomyelitis (EAE), in female mice. Similar to MS, EAE is characterized by inflammation of the central nervous system (CNS), leading to damaged myelin (demyelination) and disability in affected animals. 

EAE-affected mice were divided into groups and received a treatment of one of the following: an inert control solution, prolactin, standard MS therapy interferon-b (IFN-b) or a combination of prolactin and IFN-b. For the purpose of the study, IFN-b was given at a sub-optimal dosage to try and suppress any possible pro-inflammatory effects caused by prolactin.

Treatment efficacy was assessed using two measures: EAE clinical disease scores (a measure of tail and limb disability in the mice), and inflammation and demyelination in the animal’s spinal cord (spinal cord tissue samples were scrutinized under a microscope and indicators of inflammation and demyelination were assessed). Additionally, cells from the lymph nodes of mice were grown on culture dishes to study the effects of different doses of prolactin on the activity of pro-inflammatory immune cells.

Results

Although prolactin appeared to increase the number of pro-inflammatory immune cells in cell culture experiments, treatment with prolactin did not worsen the degree of disability or spinal cord inflammation and demyelination in EAE-affected mice. When prolactin and IFN-b were administered together, the mice displayed a marked improvement in disability, along with a reduction in spinal cord inflammation and demyelination.

Comment

The study provides evidence that prolactin, in combination with an immune modifying drug, reduces disease severity, inflammation and demyelination in animals that have an MS-like disorder. Whether this improvement is the result of enhanced remyelination remains unclear.  As the researchers note, measuring remyelination in EAE-affected mice is no simple matter as lesion development and location is unpredictable and there are still no validated measures for repair. While prolactin did not increase disease severity, the researchers suggest that any inflammatory response caused by prolactin may have been offset by IFN-β; this inference was supported by the observation that prolactin on its own increased pro-inflammatory immune cell activity.

Despite the limitations of using animals to investigate human disease, these types of early pre-clinical studies are essential basic research. They are critical to understanding the risks and benefits of potential MS therapeutics in a safe and controlled environment. Harnessing the biological factors present in pregnant and breastfeeding women, such as prolactin, that potentially repair nerve tissue and alleviate inflammation is an important strategy for the identification and subsequent development of novel MS therapeutics.

Source

Zhornitsky S et al. (2015) Prolactin in combination with interferon-b reduces disease severity in an animal model of multiple sclerosis. Journal of Neuroinflammation. 12(1):55