https://doi.org/10.3390/ vaccines9101186
Our systems biology results highlighted central signaling roles for IFN-gamma and TNF-alpha in both myocarditis and viral disease maps. Finally, combing the knowledge from searching both VAERS and MetaCoreTM enabled the exploration of age and sex differences of post-vaccine myocarditis. We found evidence in the biomedical literature indicating gender and age differences in many immunological factors. The sex differences in the levels of proinflammatory cytokines, including TNF-alpha and IFN-gamma, increase at puberty and then wane later in life suggesting hormonal effects. This goes in concert with our findings about the prevalence of post-vaccine myocarditis in the age group in adolescents and young adults (Figures 2, 3a and 4). Furthermore, Aomatsu et al. reported on the gender differences in in TNF-alpha production in human neutrophils stimulated by lipopolysaccharide (LPS) or IFN-gamma plus LPS [46]. It was suggested that the lower sensitivity of female neutrophils to LPS and IFN-gamma, was due to the anti-inflammatory effects of estradiol on vascular endothelial cells and monocytes/macrophages [46]. However, for immune response factors the sex difference remains constant from birth to old age (for example higher numbers of CD4+ T cells and higher rations of CD4/CD8 T have been reported in females at all age groups) [46].
