Fever Induced by Zymosan A and Polyinosinic-Polycytidylic Acid in Female Rats: Influence of Sex Hormones and the Participation of Endothelin-1

Coelho, Leticia; Cruz, Juliana Varella; Maba, I.K.; Zampronio, Aleksander Roberto

doi:10.1007/s10753-020-01335-5

Cited by 6 publications

(3 citation statements)

References 59 publications

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“…Considering the definite adverse event of fever as an example, the elderly were not impacted by MSC administration, perhaps because of blunt reactions of the organism to acute inflammation triggered by MSCs [ 16 ]. Women more easily suffer from transient fever, and the oestrogen level is under serious doubt [ 17 ]. The population in North America underwent transient fever less often than other regional populations, which could suggest racial discrepancies in MSC administration.…”

Section: Discussionmentioning

confidence: 99%

The safety of MSC therapy over the past 15 years: a meta-analysis

2021

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Background Despite increasing clinical investigations emphasizing the safety of mesenchymal stem cell (MSC) therapy in different populations with different diseases, no article has recently reviewed the adverse events in all populations. Aim To evaluate the safety of MSC therapy in all populations receiving MSC therapy and explore the potential heterogeneities influencing the clinical application of MSCs. Methods The PubMed, Embase, Web of Science and Scopus databases were searched from onset until 1 March 2021. Results All adverse events are displayed as odds ratios (ORs) and 95% CIs (confidential intervals). In total, 62 randomized clinical trials were included that enrolled 3546 participants diagnosed with various diseases (approximately 20 types of diseases) treated with intravenous or local implantation versus placebo or no treatment. All studies were of high quality, and neither serious publication bias nor serious adverse events (such as death and infection) were discovered across the included studies. The pooled analysis demonstrated that MSC administration was closely associated with transient fever (OR, 3.65, 95% CI 2.05–6.49, p < 0.01), administration site adverse events (OR, 1.98, 95% CI 1.01–3.87, p = 0.05), constipation (OR, 2.45, 95% CI 1.01–5.97, p = 0.05), fatigue (OR, 2.99, 95% CI 1.06–8.44, p = 0.04) and sleeplessness (OR, 5.90, 95% CI 1.04–33.47, p = 0.05). Interestingly, MSC administration trended towards lowering rather than boosting the incidence rate of arrhythmia (OR, 0.62, 95% CI 0.36–1.07, p = 0.09). Conclusions Conclusively, MSC administration was safe in different populations compared with other placebo modalities.

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Section: Discussionmentioning

confidence: 99%

The safety of MSC therapy over the past 15 years: a meta-analysis

2021

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“…Perhaps females do not need to have as strong of an activated response because they already have “more players in the game”. This layer of nuance for understanding sex differences in immune/neuroimmune function adds to the broader notion that sex differences are not just about who has a stronger response, but that the type and pattern of response matters [ 26 , 34 ], together with the context (e.g., dose, type of challenge, timing, hormonal states [ 13 , 34 , 88 , 90 ]) all of which contribute to the complexity of understanding sex differences and their functional implications. Future work will need to address whether and how sex differences in the cytokine and chemokine basal levels or activation in response to immune challenge result in modulation of neural function and contribute to sex-biases in neurological and psychiatric disease.…”

Section: Discussionmentioning

confidence: 99%

Sex differences and similarities in the neuroimmune response to central administration of poly I:C

Posillico

Garcia-Hernandez

Tronson

2021

J Neuroinflammation

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Background The neuroimmune system is required for normal neural processes, including modulation of cognition, emotion, and adaptive behaviors. Aberrant neuroimmune activation is associated with dysregulation of memory and emotion, though the precise mechanisms at play are complex and highly context dependent. Sex differences in neuroimmune activation and function further complicate our understanding of its roles in cognitive and affective regulation. Methods Here, we characterized the physiological sickness and inflammatory response of the hippocampus following intracerebroventricular (ICV) administration of a synthetic viral mimic, polyinosinic:polycytidylic acid (poly I:C), in both male and female C57Bl/6N mice. Results We observed that poly I:C induced weight loss, fever, and elevations of cytokine and chemokines in the hippocampus of both sexes. Specifically, we found transient increases in gene expression and protein levels of IL-1α, IL-1β, IL-4, IL-6, TNFα, CCL2, and CXCL10, where males showed a greater magnitude of response compared with females. Only males showed increased IFNα and IFNγ in response to poly I:C, whereas both males and females exhibited elevations of IFNβ, demonstrating a specific sex difference in the anti-viral response in the hippocampus. Conclusion Our data suggest that type I interferons are one potential node mediating sex-specific cytokine responses and neuroimmune effects on cognition. Together, these findings highlight the importance of using both males and females and analyzing a broad set of inflammatory markers in order to identify the precise, sex-specific roles for neuroimmune dysregulation in neurological diseases and disorders.

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“…Take the de nite side event fever as an instance, the aged were not susceptible to MSC administration and this may be because of blunt reactions of the organism to acute in ammation triggered by MSC [16] . The female more easily suffers from transient fever and the estrogen level is under serious doubt [17] . The population in North America less undergo transient fever compared to other regional populations and this may suggest the racial discrepancy of MSC administration.…”

Section: Summary Of Evidencementioning

confidence: 99%

Clinical Lessons of MSC Therapy Over the Past 15 Years: A Systematic Review and Meta-Analysis

Wang¹,

Yi²,

Song³

2021

Preprint

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Background: Despite increasing clinical investigations in emphasizing the safety of MSC therapy in different populations with different diseases, recently, no article overall reviewed the side events in all populations.Aim: To evaluate the safety of MSC therapy in all populations receiving MSC therapy and explore the potential heterogeneities influencing the clinical application of MSC.Methods: The databases of PubMed, Embase, Web of Science and Scopus were searched from onset until March 1st, 2021. Results: All side events were displayed as odds ratio (OR) and 95% CI (confidential intervals). Totally, 62 randomized clinical trials (RCTs) that enrolled 3546 participants diagnosed with various diseases (about 20 kinds of diseases) treated with intravenous or local implantation vs placebo, or no treatment were included. All studies were high quality, neither serious publication bias nor serious adverse events (such as death and infection) were discovered across included studies. The pooled analysis demonstrated that MSC administration was extremely associated with transient fever [OR, 3.65, 95% CI: 2.05 to 6.49, p<0.01], administration site conditions [OR, 1.98, 95% CI: 1.01 to 3.87, p=0.05], constipation [OR, 2.45, 95% CI: 1.01 to 5.97, p=0.05], fatigue [OR, 2.99, 95% CI: 1.06 to 8.44, p=0.04], and sleeplessness [OR, 5.90, 95% CI: 1.04 to 33.47, p=0.05]. Interestingly, MSC administration trended to lower rather than boost the incidence rate of arrhythmia [OR, 0.62, 95% CI: 0.36 to 1.07, p=0.09]. Conclusions: Conclusively, MSC administration was safe in different populations compared with the other placebo modalities.

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Fever Induced by Zymosan A and Polyinosinic-Polycytidylic Acid in Female Rats: Influence of Sex Hormones and the Participation of Endothelin-1

Cited by 6 publications

References 59 publications

The safety of MSC therapy over the past 15 years: a meta-analysis

The safety of MSC therapy over the past 15 years: a meta-analysis

Sex differences and similarities in the neuroimmune response to central administration of poly I:C

Clinical Lessons of MSC Therapy Over the Past 15 Years: A Systematic Review and Meta-Analysis

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