Infection-Related Exacerbations in Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disorder in which immune-mediated demyelination and neurodegeneration drive episodic neurological deficits known as relapses. Epidemiological studies indicate that peripheral infections—particularly of the respiratory and urinary tracts—can nearly double the short-term risk of relapse. Mechanistic investigations point to several convergent pathways: systemic activation of the acute phase response generates proinflammatory cytokines that cross a compromised blood–brain barrier, reactivating microglia and recruiting autoreactive T cells; molecular mimicry between microbial and myelin antigens can precipitate bystander activation; and sustained low-grade inflammation may accelerate axonal loss and tissue atrophy. Animal models of chronic-relapsing experimental encephalomyelitis have demonstrated that hepatic chemokines, notably CXCL-1, are sufficient to reactivate central lesions and provoke clinical symptoms. Clinically, infection-related relapses contribute to cumulative disability, emphasising the need for vigilant infection control, tailored vaccination strategies and therapeutic approaches that modulate systemic inflammation without compromising central immunosurveillance.

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Infection-Related Exacerbations in Multiple Sclerosis publication trend

The graph below shows the total number of articles in infection-related exacerbations in multiple sclerosis across all publications each year (not limited to Nature Index journals).

Technical terms

Acute phase response: A systemic reaction to infection or injury characterised by hepatic production of chemokines, cytokines and acute phase proteins.

Blood–brain barrier: A selective endothelial interface that regulates passage of cells and molecules between the peripheral circulation and the central nervous system.

Relapse: An acute episode of neurological dysfunction in MS, typically lasting ≥24 hours and separated from prior events by ≥30 days.

Expanded Disability Status Scale (EDSS): A standardised scale for quantifying disability in MS, ranging from 0 (normal) to 10 (death due to MS).

Demyelination: The loss or damage of myelin sheaths surrounding axons, leading to impaired electrical conduction.

Microglia: Resident innate immune cells of the central nervous system that become activated during inflammation or injury.

References

1. Systemic inflammation associates with and precedes cord atrophy in progressive multiple sclerosis. Brain Communications (2024).
2. The contribution of the acute phase response to the pathogenesis of relapse in chronic-relapsing experimental autoimmune encephalitis models of multiple sclerosis. Journal of Neuroinflammation (2017).
3. Infection as an Environmental Trigger of Multiple Sclerosis Disease Exacerbation. Frontiers in Immunology (2015).
4. Clinically Manifest Infections Do Not Increase the Relapse Risk in People with Multiple Sclerosis Treated with Disease-Modifying Therapies: A Prospective Study †. Journal of Clinical Medicine (2023).
5. Does COVID-19 increase the long-term relapsing-remitting multiple sclerosis clinical activity? A cohort study. BMC Neurology (2022).
6. Autoantigen cross-reactive environmental antigen can trigger multiple sclerosis-like disease. Journal of Neuroinflammation (2015).