The immunomodulatory effect of oral NaHCO3 is mediated by the splenic nerve: multivariate impact revealed by artificial neural networks.

Stimulation of the inflammatory reflex (IR) is a promising strategy for treating systemic inflammatory disorders. Recent studies suggest oral sodium bicarbonate (NaHCO3) as a potential activator of the IR, offering a safe and cost-effective treatment approach. However, the mechanisms underlying NaHCO3-induced anti-inflammatory effects remain unclear. We investigated whether oral NaHCO3's immunomodulatory effects are mediated by the splenic nerve. Female rats received NaHCO3 or water (H2O) for four days, and splenic immune markers were assessed using flow cytometry. NaHCO3 led to a significant increase (p < 0.05, and/or partial eta squared > 0.06) in anti-inflammatory markers, including CD11bc + CD206 + (M2-like) macrophages, CD3 + CD4 + FoxP3 + cells (Tregs), and Tregs/M1-like ratio. Conversely, proinflammatory markers, such as CD11bc + CD38 + TNFα + (M1-like) macrophages, M1-like/M2-like ratio, and SSChigh/SSClow ratio of FSChighCD11bc + cells, decreased in the spleen following NaHCO3 administration. These effects were abolished in spleen-denervated rats, suggesting the necessity of the splenic nerve in mediating NaHCO3-induced immunomodulation. Artificial neural networks accurately classified NaHCO3 and H2O treatment in sham rats but failed in spleen-denervated rats, highlighting the splenic nerve's critical role. Additionally, spleen denervation independently influenced Tregs, M2-like macrophages, Tregs/M1-like ratio, and CD11bc + CD38 + cells, indicating distinct effects from both surgery and treatment. Principal component analysis (PCA) further supported the separate effects. Our findings suggest that the splenic nerve transmits oral NaHCO3-induced immunomodulatory changes to the spleen, emphasizing NaHCO3's potential as an IR activator with therapeutic implications for a wide spectrum of systemic inflammatory conditions.

Can a basic solution activate the inflammatory reflex? A review of potential mechanisms, opportunities, and challenges.

Stimulation of the inflammatory reflex (IR) is a promising strategy to treat systemic inflammatory disorders. However, this strategy is hindered by the cost and side effects of traditional IR activators. Recently, oral intake of sodium bicarbonate (NaHCO3) has been suggested to activate the IR, providing a safe and inexpensive alternative. Critically, the mechanisms whereby NaHCO3 might achieve this effect and more broadly the pathways underlying the IR remain poorly understood. Here, we argue that the recognition of NaHCO3 as a potential IR activator presents exciting clinical and research opportunities. To aid this quest, we provide an integrative review of our current knowledge of the neural and cellular pathways mediating the IR and discuss the status of physiological models of IR activation. From this vantage point, we derive testable hypotheses on potential mechanisms whereby NaHCO3 might stimulate the IR and compare NaHCO3 with classic IR activators. Elucidation of these mechanisms will help determine the therapeutic value of NaHCO3 as an IR activator and provide new insights into the IR circuitry.

Predictors of overlapping autoimmune disease in Neuromyelitis Optica Spectrum disorder (NMOSD): A retrospective analysis in two inner-city hospitals.

BACKGROUND: The coexistence of Neuromyelitis Optica spectrum disorder (NMOSD) with other autoimmune diseases (AD-NMOSD) presents worse clinical outcomes and healthcare costs than NMOSD alone (NMOSD-only). NMOSD and other autoimmune diseases also have a higher prevalence and morbidity in Black. We aim to compare clinical features and treatment responses in NMOSD patients with and without overlapping autoimmunity in a predominantly Black cohort. We further identify predictors associated with each clinical subtype. METHODS: AD-NMOSD (n = 14) and NMOSD-only (n = 27) patients were identified retrospectively. Demographic, clinical, laboratory, imaging, and response to treatment data were examined. RESULTS: Our cohort was predominately Black (82.9%). The prevalence of grouped-comorbidities, history of infections, sensory symptoms, Expanded Disability Status Scale (EDSS) before treatment, double-stranded DNA, antinuclear, ribonucleoprotein, and antiphospholipid antibodies, spinal-cord edema, white matter occipital lesions, and the levels of C-reactive protein, urine protein/creatinine, white blood cell count in cerebrospinal fluid (CSF), were higher in AD-NMOSD patients (p < 0.05 and/or Cramer's V > 30, Cohen's d > 50), whereas the age of males, visual symptoms, serum albumin, platelet count, and optic nerve enhancement were lower. EDSS after treatment improved in both groups being more evident in NMOSD-only patients (p = 0.003, SE = 0.58 vs p = 0.075, SE = 0.51). Other variables had a close to moderate SE, and others did not differ between NMOSD subtypes. A higher frequency of grouped-comorbidities, lower serum albumin, and platelet count were independently associated with a higher risk for AD-NMOSD. CONCLUSIONS: Some clinical features between AD-NMOSD and NMOSD-only patients were similar, while others differed. Comorbidities, serum albumin, and platelet count may be independent predictors of AD-NMOSD.

Assessment of interstitial lung disease among black rheumatoid arthritis patients.

BACKGROUND: Conflicting reports exist regarding the racial and the gender distribution of rheumatoid arthritis-related interstitial lung disease (RA-ILD). In a major population study of predominately Whites, RA-ILD was reported mainly among smoker middle-aged men. However, recent data suggest that the disease is that of elderly women. Our study aimed to assess the prevalence and identify the gender differences and clinical characteristics of RA-ILD in a predominantly Black population. METHODS: Cross-sectional analysis of data obtained from the records of 1142 patients with RA diagnosis by ICD codes of which 503 cases met the inclusion criteria for the study. Eighty-six patients had chronic respiratory symptoms of cough and dyspnea and were further assessed by our multidisciplinary group of investigators. Thirty-two subjects with an established diagnosis of rheumatoid arthritis met the diagnostic criteria for interstitial lung disease. RESULTS: Of the 32 patients with RA-ILD, mean age was 62.6 ± 2.2 (± SEM), 93.7% were females, and 89% Blacks with a BMI = 29.2 (Kg/m2). Usual interstitial pneumonia (UIP) was found in 24/32 (75%) of the cases. Seventy-two percent of the RA-ILD patient had seropositive RA. Smoking history was reported in 31.3% of the cohort, gastroesophageal reflux disease (GERD) in 32.3%, and cardiovascular disease (CVD) risk factors in 65.6%. CONCLUSION: Our study indicates RA-ILD among Blacks is predominantly a disease of elderly females with higher rates of GERD and CVD risk factors. Further studies are needed to identify the pathogenetic differences accounting for the gender distribution of RA-ILD among Black and White populations.Key Points• First study to assess ILD among predominantly Black RA patients.• The prevalence of RA-associated ILD was 6.36%, affecting mostly women in their sixth decade with seropositive disease.• COPD was the most common airway disease among non-RA-ILD Black population.• GERD was found in approximately one-third of patients with RA-associated ILD versus one-fifth of those RA patients without any lung disease.

Rheumatoid Arthritis in Sickle-Cell Population: Pathophysiologic Insights, Clinical Evaluation and Management.

The advent of hydroxyurea and advanced medical care, including immunizations has led to improved survival among patients with Sickle Cell Disease (SCD). This prolonged survival however, introduces a chronic inflammatory disorder, Rheumatoid Arthritis (RA), which presents at a relatively older age and is rarely reported among SCD patients. In this review, we highlight the epidemiological association of SCD-RA and discuss the underlying common pathogenetic mechanisms, such as endothelial dysfunction, the role of inflammatory cytokines and oxidative stress. We also point to the difficulties in ascertaining the clinical diagnosis of RA in SCD patients. Finally, we provide rationale for therapeutic options available for RA and the challenges in the management of these patients with agents that are known to increase the risk of infection and immunosuppression such as steroids, disease modifying anti-rheumatic drugs and biologics.