Men Have a Stronger Monocyte-Derived Cytokine Production Response upon Stimulation with the Gram-Negative Stimulus Lipopolysaccharide than Women: A Pooled Analysis Including 15 Study Populations

Beenakker, Karel G M; Westendorp, Rudi G.J.; Craen, Anton J. M. de; Chen, Sijia; Raz, Yotam; Ballieux, Bart E.; Nelissen, Rob G H H; Later, Alexander F.L.; Huizinga, Tom W J; Slagboom, P. Eline; Boomsma, Dorret I.; Maier, Andrea B.

doi:10.1159/000499840

Cited by 46 publications

(39 citation statements)

References 48 publications

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“… 2 Indeed, several groups have found sex differences in the immune response, including the innate immune response. 78 79 Regarding COVID-19, there are indications that immune response (inflammation) markers such as interleukin-6 (IL-6) are associated with severity and mortality. 80 81 In a broader perspective, immune response markers, such as IL-6, have also been associated with worse outcome and higher mortality in trauma patients.…”

Section: Discussionmentioning

confidence: 99%

Demographic risk factors for COVID-19 infection, severity, ICU admission and death: a meta-analysis of 59 studies

et al. 2021

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ObjectiveWe aimed to describe the associations of age and sex with the risk of COVID-19 in different severity stages ranging from infection to death.DesignSystematic review and meta-analysis.Data sourcesPubMed and Embase through 4 May 2020.Study selectionWe considered cohort and case–control studies that evaluated differences in age and sex on the risk of COVID-19 infection, disease severity, intensive care unit (ICU) admission and death.Data extraction and synthesisWe screened and included studies using standardised electronic data extraction forms and we pooled data from published studies and data acquired by contacting authors using random effects meta-analysis. We assessed the risk of bias using the Newcastle-Ottawa Scale.ResultsWe screened 11.550 titles and included 59 studies comprising 36.470 patients in the analyses. The methodological quality of the included papers was high (8.2 out of 9). Men had a higher risk for infection with COVID-19 than women (relative risk (RR) 1.08, 95% CI 1.03 to 1.12). When infected, they also had a higher risk for severe COVID-19 disease (RR 1.18, 95% CI 1.10 to 1.27), a higher need for intensive care (RR 1.38, 95% CI 1.09 to 1.74) and a higher risk of death (RR 1.50, 95% CI 1.18 to 1.91). The analyses also showed that patients aged 70 years and above have a higher infection risk (RR 1.65, 95% CI 1.50 to 1.81), a higher risk for severe COVID-19 disease (RR 2.05, 95% CI 1.27 to 3.32), a higher need for intensive care (RR 2.70, 95% CI 1.59 to 4.60) and a higher risk of death once infected (RR 3.61, 95% CI 2.70 to 4.84) compared with patients younger than 70 years.ConclusionsMeta-analyses on 59 studies comprising 36.470 patients showed that men and patients aged 70 and above have a higher risk for COVID-19 infection, severe disease, ICU admission and death.PROSPERO registration numberCRD42020180085.

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Section: Discussionmentioning

confidence: 99%

Demographic risk factors for COVID-19 infection, severity, ICU admission and death: a meta-analysis of 59 studies

et al. 2021

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“…Monocyte function is sex specific and absolute numbers of monocytes have been shown to be higher in males than females (45). Several studies have also reported more robust cytokine production in male compared with female monocytes (46)(47)(48). Sex hormones impact immune cell function.…”

Section: Discussionmentioning

confidence: 99%

Time Course of Peripheral Leukocytosis and Clinical Outcomes After Aneurysmal Subarachnoid Hemorrhage

et al. 2021

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Objective: Systemic inflammation after subarachnoid hemorrhage (SAH) is implicated in delayed cerebral ischemia (DCI) and adverse clinical outcomes. We hypothesize that early changes in peripheral leukocytes will be associated with outcomes after SAH.Methods: SAH patients admitted between January 2009 and December 2016 were enrolled into a prospective observational study and were assessed for Hunt Hess Scale (HHS) at admission, DCI, and modified Ranked Scale (mRS) at discharge. Total white blood cell (WBC) counts and each component of the differential cell count were determined on the day of admission (day 0) to 8 days after bleed (day 8). Global cerebral edema (GCE) was assessed on admission CT, and presence of any infection was determined. Statistical tests included student's t-test, Chi-square test, and multivariate logistic regression (MLR) models.Results: A total of 451 subjects were analyzed. Total WBCs and neutrophils decreased initially reaching a minimum at day 4–5 after SAH. Monocyte count increased gradually after SAH and peaked between day 6–8, while basophils and lymphocytes decreased initially from day 0 to 1 and steadily increased thereafter. Neutrophil to lymphocyte ratio (NLR) reached a peak on day 1 and decreased thereafter. WBCs, neutrophils, monocytes, and NLR were higher in patients with DCI and poor functional outcomes. WBCs, neutrophils, and NLR were higher in subjects who developed infections. In MLR models, neutrophils and monocytes were associated with DCI and worse functional outcomes, while NLR was only associated with worse functional outcomes. Occurrence of infection was associated with poor outcome. Neutrophils and NLR were associated with infection, while monocytes were not. Monocytes were higher in males, and ROC curve analysis revealed improved ability of monocytes to predict DCI and poor functional outcomes in male subjects.Conclusions: Monocytosis was associated with DCI and poor functional outcomes after SAH. The association between neutrophils and NLR and infection may impact outcomes. Early elevation in monocytes had an improved ability to predict DCI and poor functional outcomes in males, which was independent of the occurrence of infection.

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“…Finally, recent findings indicate a sexual dimorphism in the activation and regulation of a broad spectrum of peripheral cytokines and cytokine pathways. Several studies, for example, have described a more robust monocyte-derived cytokine production upon ex vivo stimulation with lipopolysaccharides (LPS) in men than in women ( 167 – 169 ), although others have found no sex differences ( 170 , 171 ). Studies in mice also report that cytokine response of CD4 + T cells generally varies between males and females, with females displaying the highest Th1, Th2, and Tregs responses, contingent upon the stage of infection or type of antigen encountered ( 172 – 175 ).…”

Section: Biology Of Sex Differences In Multiple Sclerosismentioning

confidence: 99%

SeXX Matters in Multiple Sclerosis

2020

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Multiple sclerosis (MS) is the most common chronic inflammatory and neurodegenerative disease of the central nervous system (CNS). An interesting feature that this debilitating disease shares with many other inflammatory disorders is that susceptibility is higher in females than in males, with the risk of MS being three times higher in women compared to men. Nonetheless, while men have a decreased risk of developing MS, many studies suggest that males have a worse clinical outcome. MS exhibits an apparent sexual dimorphism in both the immune response and the pathophysiology of the CNS damage, ultimately affecting disease susceptibility and progression differently. Overall, women are predisposed to higher rates of inflammatory relapses than men, but men are more likely to manifest signs of disease progression and worse CNS damage. The observed sexual dimorphism in MS may be due to sex hormones and sex chromosomes, acting in parallel or combination. In this review, we outline current knowledge on the sexual dimorphism in MS and discuss the interplay of sex chromosomes, sex hormones, and the immune system in driving MS disease susceptibility and progression.

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Men Have a Stronger Monocyte-Derived Cytokine Production Response upon Stimulation with the Gram-Negative Stimulus Lipopolysaccharide than Women: A Pooled Analysis Including 15 Study Populations

Cited by 46 publications

References 48 publications

Demographic risk factors for COVID-19 infection, severity, ICU admission and death: a meta-analysis of 59 studies

Demographic risk factors for COVID-19 infection, severity, ICU admission and death: a meta-analysis of 59 studies

Time Course of Peripheral Leukocytosis and Clinical Outcomes After Aneurysmal Subarachnoid Hemorrhage

SeXX Matters in Multiple Sclerosis

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