Does MS Raise White Blood Cell Count?

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system, leading to a range of neurological symptoms. Since MS involves immune system dysfunction, many wonder whether it influences white blood cell (WBC) counts, which play a crucial role in immune responses.

Understanding how MS impacts WBC levels provides insight into disease activity, inflammation, and treatment effects.

Immune Dysregulation in MS

MS is characterized by an abnormal immune response that targets the central nervous system, leading to demyelination and neuroinflammation. This dysregulation involves autoreactive T cells, B cells, and innate immune components that mistakenly attack myelin, the protective sheath surrounding nerve fibers. Unlike infections that trigger temporary immune responses, MS involves persistent immune misdirection, affecting various hematological parameters, including WBC counts.

T cells, particularly CD4+ and CD8+ subsets, play a central role in MS pathology. Research shows an imbalance between pro-inflammatory Th1 and Th17 cells and regulatory T cells (Tregs), which normally suppress excessive immune activation. A study in Nature Reviews Immunology (2023) highlighted that reduced Treg function in MS contributes to sustained inflammation, potentially affecting circulating WBC levels. B cells, once considered secondary players, are now recognized as major contributors to disease progression. These cells not only produce autoantibodies but also secrete pro-inflammatory cytokines that amplify immune responses, further influencing hematological profiles.

Innate immune cells, such as monocytes and neutrophils, also show altered behavior in MS. Elevated monocyte activation has been observed in both relapsing-remitting and progressive forms of the disease, as reported in a 2024 Lancet Neurology study. These cells infiltrate the central nervous system and release inflammatory mediators that perpetuate tissue damage. Neutrophils, though less studied in MS, contribute to blood-brain barrier disruption, which may indirectly affect WBC distribution in circulation.

White Blood Cell Count Fluctuations

WBC counts in MS patients fluctuate depending on disease phase, individual variability, and external influences. While some maintain normal levels, others experience deviations that may be transient or persistent. These fluctuations arise from physiological responses to disease activity, interactions with therapies, or secondary factors such as infections and stress. Unlike conditions that consistently elevate or suppress WBC counts, MS presents a complex hematological picture where trends must be interpreted in context.

Longitudinal studies tracking hematological changes in MS patients report variability in WBC counts, particularly during relapses. A 2023 study in JAMA Neurology found that some relapsing-remitting MS patients exhibited temporary leukocytosis—an increase in WBC count—coinciding with symptom exacerbations. This rise was attributed to systemic responses associated with active disease episodes. Conversely, a subset demonstrated mild leukopenia, characterized by reduced WBC levels, more common in those receiving immunomodulatory treatments. These findings underscore that WBC counts alone do not provide a definitive measure of MS progression but reflect a dynamic interplay of factors.

Beyond relapse-related changes, WBC fluctuations in MS can be influenced by physiological stressors, lifestyle factors, and secondary conditions. Chronic stress, linked to MS exacerbations, triggers hormonal pathways involving cortisol and the hypothalamic-pituitary-adrenal axis, affecting WBC levels. Infections—bacterial or viral—can temporarily elevate WBC counts, complicating the interpretation of routine blood tests. Given MS patients’ altered immune landscape, distinguishing between disease-related hematological changes and responses to external stimuli requires careful evaluation.

Inflammation Patterns

Inflammation in MS follows a fluctuating course, with periods of heightened activity interspersed with phases of relative stability. This variability stems from dynamic processes within the central nervous system, where inflammatory cascades contribute to both acute symptom flare-ups and long-term disease progression. Some individuals experience episodic inflammation marked by relapses, while others develop a more continuous inflammatory state, leading to gradual neurological decline.

Advanced imaging techniques, such as magnetic resonance imaging (MRI) with gadolinium contrast, provide insights into MS-related inflammation. Active lesions, appearing as contrast-enhancing areas on MRI scans, indicate localized inflammatory activity and often correlate with worsening symptoms. However, inflammation is not always confined to these visible lesions. Studies using positron emission tomography (PET) imaging have revealed diffuse inflammatory activity even in regions appearing normal on standard MRI scans, suggesting inflammation extends beyond discrete focal sites and may contribute to widespread neurodegeneration.

Neuroglial interactions shape the persistence of inflammation in MS. Microglia, the central nervous system’s resident immune cells, sustain inflammatory responses by releasing pro-inflammatory mediators, perpetuating tissue damage even in the absence of overt symptoms. This chronic, low-grade inflammation has been implicated in progressive MS, contributing to ongoing neuroaxonal injury. Unlike the transient inflammation seen in relapsing-remitting MS, this sustained inflammatory environment can lead to irreversible neuronal loss, highlighting the need for therapies targeting both acute and chronic inflammation.

Assessing White Blood Cell Levels

Evaluating WBC levels in MS requires a nuanced approach, as fluctuations arise from various physiological and external factors. A routine complete blood count (CBC) provides an initial measure, but interpreting values in the context of MS necessitates tracking trends over time rather than relying on isolated readings. Physicians monitor WBC levels longitudinally to identify patterns corresponding with symptom changes, treatment effects, or secondary conditions. While normal WBC counts typically range between 4,000 and 11,000 cells per microliter of blood, deviations in MS patients may not always indicate disease progression or complications.

Hematological markers within the WBC profile offer additional insights. Differential counts break down proportions of neutrophils, lymphocytes, monocytes, eosinophils, and basophils, clarifying whether fluctuations stem from immune modulation, infection, or systemic inflammation. A shift in lymphocyte levels may signal immune suppression from disease-modifying therapies, whereas elevated neutrophils could indicate an acute inflammatory response. Additionally, absolute lymphocyte counts (ALCs) help monitor risks associated with immunosuppressive treatments, as critically low levels increase infection susceptibility.

Treatment Effects on White Blood Cell Profiles

The impact of MS treatments on WBC profiles varies depending on each therapy’s mechanism of action. Disease-modifying treatments (DMTs) modulate immune activity, influencing WBC counts by suppressing certain immune cell populations or altering their function. Because these therapies target different aspects of immune regulation, their effects range from mild fluctuations to significant reductions requiring monitoring. Understanding these changes is essential for balancing treatment efficacy with potential risks, such as increased infection susceptibility or hematological complications.

Common DMTs, including fingolimod, ocrelizumab, and alemtuzumab, have well-documented effects on WBC counts. Fingolimod, a sphingosine-1-phosphate receptor modulator, sequesters lymphocytes in lymphoid tissues, reducing circulating lymphocyte levels. This effect is often reversible upon discontinuation but requires monitoring to prevent complications. Ocrelizumab, a monoclonal antibody targeting CD20-expressing B cells, depletes a specific subset of lymphocytes while sparing other immune cells, lowering WBC counts without causing broad immunosuppression. Alemtuzumab induces profound lymphocyte depletion that can persist for months or even years, necessitating long-term surveillance for infections and secondary autoimmune reactions. The degree of WBC suppression varies, emphasizing the need for personalized monitoring protocols.

Other Health Factors

Beyond MS and its treatments, various health factors influence WBC levels, complicating blood test interpretations. Lifestyle choices, underlying medical conditions, and infections all shape hematological profiles. Given MS patients’ immune dysregulation, these additional variables must be considered to avoid misattributing changes solely to the disease or its therapies.

Chronic stress, sleep disturbances, and poor nutrition can alter WBC levels. Psychological stress triggers cortisol release, suppressing certain immune functions and leading to transient leukopenia. Sleep deprivation has been linked to immune changes, with studies indicating inadequate rest reduces lymphocyte counts while increasing inflammatory markers. Additionally, deficiencies in essential nutrients such as vitamin B12, iron, and folate impair bone marrow function, reducing WBC production.

Infections significantly influence WBC levels, particularly in immunosuppressed individuals. Viral infections, such as Epstein-Barr virus or cytomegalovirus, can cause transient leukopenia, while bacterial infections often lead to leukocytosis. Given MS patients’ altered immune response, distinguishing between disease-related WBC changes and those triggered by external pathogens is essential. Regular monitoring and proactive infection management help minimize complications while ensuring WBC fluctuations are interpreted within the appropriate clinical context.