| Visceral obesity (secretion of inflammatory cytokines, chemokines, adipokines) |
Activation of the innate immune cells by pathogen-associated molecular patterns and damage-associated molecular patterns |
Posttranslational alterations (at the level of micro-RNA) |
| Latent infections (cytomegalovirus, helicobacter pylori) |
Cell senescence (a senescence-associated secretory phenotype: intracellular signaling loops and inflammatory cascade involving the nuclear factor kappa-B, IL-1α, transforming growth factor-betta and IL-6 pathway) |
Mitochondrial dysfunction (oxydative-stress mediated inflammation via activation of nod-like receptor 3 inflammasome) |
| Depression, chronic stress (via activation of the hypothalamus-hypophysis-adrenal stress axis) |
Cell apoptosis-transformation into necrotic cells |
Impaired autophagy (impaired clearance of apoptotic cells) |
| Comorbidities (tissue infiltration with inflammatory cells, paracrine cell activation) |
Cell surfice receptors density and activation alterations |
Transcription factors activation in inflammatory response pathways (nuclear factor kappa-B, activation protein-1) |
| Neuro-endocrine alterations |
|
Dysregulation of paroxisome proliferator activated receptors (nuclear hormone receptors activated by fatty acids and oic osano ides) |
| Renal function decline |
|
Dysregulation of pro-resolving lipid mediators (lipoxins, resolvins, maresins) |
| Altered permeability of the gastro-intestinal system |
|
M1 (pro-inflammatory) type macrophages |
| Alterations in gut microbiome |
|
Insufficient inflammation resolution |
| Genetic predisposition |
|
An imbalance between pro-inflammatory TNF-α, IL-6, IL-18, IL-1 cytokine family (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, and IL-36γ), IL-17A, IL-22, and anti-inflammatory cytokines IL-10, IL-37, transforming growth factor-betta, sTNFR, sIL-1R |
