Magnesium and Inflammatory Diseases

A new study published in The Journal of Immunology suggests that magnesium sulfate, used to treat preeclamspia in preterm labor, may also decrease inflammation and become a therapy for inflammatory diseases.

Researchers at Case Western Reserve University School of Medicine recently discovered the mechanism by which magnesium reduces the production of cytokines. Cytokines are molecules responsible for regulating inflammation; they play a key in role conditions such as diabetes, obesity, atherosclerosis, asthma, and alcoholic liver disease and cirrhosis. Although the study was related to pregnancy, inflammation is the culprit of many conditions and learning more about individual’s magnesium levels may help a much broader patient population.

In a study published in The Journal of Immunology, the laboratories of Helene Bernstein, MD, PhD, and Andrea Romani, MD, PhD, reported that magnesium decreases inflammation by reducing the activity of cells’ primary protein, Nuclear Factor Kappa Beta (NF-kB), and the subsequent production of cytokines. This new insight offers a promising new immunotherapeutic strategy by which a simple nutrient, known to be safe based on its extensive usage in obstetric settings, can decrease inflammation in diseases other than pregnancy, including sepsis, respiratory distress syndrome, asthma, atherosclerosis, diabetes and cancer. The cost of all of these diseases in the United States exceeds $200 billion annually.

“The concept that [magnesium] decreases inflammation is exciting and relevant to other diseases. Now that we understand how magnesium functions, we can figure out how to make it work even better,” says Dr. Bernstein, associate professor of reproductive biology and molecular biology and microbiology, Case Western Reserve School of Medicine, OB/GYN at University Hospitals MacDonald Women’s Hospital, and senior author of the study.

Permission granted to post excerpts from original article
by Emily Sutherlin – Childbirth Educator
Indianapolis Autoimmune Disease Examiner.

Magnesium Decreases Inflammatory Cytokine Production: A Novel innate Immunomodulatory Mechanism

Source:

J Immunol. 2012 Jun 15;188(12):6338-46.
Sugimoto J, Romani AM, Valentin-Torres AM, Luciano AA, Ramirez Kitchen CM, Funderburg N, Mesiano S, Bernstein HB.Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.

Abstract:

MgSO(4) exposure before preterm birth is neuroprotective, reducing the risk of cerebral palsy and major motor dysfunction. Neonatal inflammatory cytokine levels correlate with neurologic outcome, leading us to assess the effect of MgSO(4) on cytokine production in humans. We found reduced maternal TNF-? and IL-6 production following in vivo MgSO(4) treatment. Short-term exposure to a clinically effective MgSO(4) concentration in vitro substantially reduced the frequency of neonatal monocytes producing TNF-? and IL-6 under constitutive and TLR-stimulated conditions, decreasing cytokine gene and protein expression, without influencing cell viability or phagocytic function. In summary, MgSO(4) reduced cytokine production in intrapartum women, term and preterm neonates, demonstrating effectiveness in those at risk for inflammation-associated adverse perinatal outcomes. By probing the mechanism of decreased cytokine production, we found that the immunomodulatory effect was mediated by magnesium and not the sulfate moiety, and it was reversible. Cellular magnesium content increased rapidly upon MgSO(4) exposure, and reduced cytokine production occurred following stimulation with different TLR ligands as well as when magnesium was added after TLR stimulation, strongly suggesting that magnesium acts intracellularly. Magnesium increased basal I?B? levels, and upon TLR stimulation was associated with reduced NF-?B activation and nuclear localization. These findings establish a new paradigm for innate immunoregulation, whereby magnesium plays a critical regulatory role in NF-?B activation, cytokine production, and disease pathogenesis.