Combined Use of Intranasal Methylprednisolone and Allopregnanolone: Revisiting Anti-inflammatory and Remyelinating Treatment in a Murine Model of Multiple Sclerosis.

Background: Multiple sclerosis (MS) is a demyelinating, neuroinflammatory, progressive disease that severely affects human health of young adults. Neuroinflammation (NI) and demyelination, as well as their interactions, are key therapeutic targets to halt or slow disease progression. Potent steroidal anti-inflammatory drugs such as methylprednisolone (MP) and remyelinating neurosteroids such as allopregnanolone (ALLO) could be co-administered intranasally to enhance their efficacy by providing direct access to the central nervous system (CNS).

A Glucocorticoid-Mediated Immunoregulatory Circuit Integrated at Brain Levels: Our Early Studies and a Present View.

Background: It was known since the 1940s that pharmacological administration of glucocorticoids can inhibit inflammatory and immune processes, and these hormones are still today among the most widely used therapeutic tools to treat diseases with immune components. However, it became clear later that endogenous glucocorticoids can either support or restrain immune processes.

Summary: Early studies showed that (a) endogenous levels of glucocorticoids can modulate immune cell activity; (b) the immune response itself can stimulate the hypothalamus-pituitary-adrenal (HPA) axis to release glucocorticoids to levels that can exert immunoregulatory effects; (c) immune products, later identified as cytokines, mediate this effect.

Intranasal Versus Intravenous Dexamethasone to Treat Hospitalized COVID-19 Patients: A Randomized Multicenter Clinical Trial.

Background: SARS-CoV2 induces flu-like symptoms that can rapidly progress to severe acute lung injury and even death. The virus also invades the central nervous system (CNS), causing neuroinflammation and death from central failure. Intravenous (IV) or oral dexamethasone (DXM) reduced 28 d mortality in patients who required supplemental oxygen compared to those who received conventional care alone.

Sympathetic-Immune Interactions during Different Types of Immune Challenge.

Background: The neuro-endocrine regulation of immune functions is based on a complex network of interactions. As part of this series of articles, we refer here to immune-sympathetic interactions that are triggered by different types of immune challenge.

Summary: We mention the initial hypothesis that led to the proposal that the sympathetic nervous system (SNS) is involved in immunoregulation.