Table 2.
Cytokines in calcific aortic valve disease
| Cytokine | Immunological Role | Finding | References |
|---|---|---|---|
| Acute phase reactants | |||
| IL-1β | Acute phase reactant | ↑ in CAVD; ↑ in valves with more severe remodeling | (76) |
| IL-1R antagonist | Opposes IL-1 activity | ↓ in AS | (88) |
| IL-6 | Acute phase reactant; promotes T-cell maturation | ↑ in CAVD; ↑ in valves with more severe remodeling; IL6R SNP decreases severity of AS | (45, 170, 184) |
| TNFα | Acute phase reactant | ↑ in CAVD; ↑ with increased inflammation in the valve | (77, 170) |
| Chemokines | |||
| CCL11 | Recruits eosinophils | ↑ in CAVD | (57, 152) |
| CCL19 | Recruits CCR7+ dendritic cells and T cells | ↑ in CAVD | (152) |
| CCL21 | Recruits CCR7+ T cells | ↑ in CAVD | (152) |
| CXCL5 | Recruits angiogenic neutrophils | ↑ in CAVD | (57, 152) |
| CXCL9 | Recruits T cells | ↑ in CAVD | (152) |
| Promoters of specific cell-type maturation | |||
| IFNγ | Acute phase reactant; promotes Th1 maturation | ↑ in CAVD | (123) |
| IL-33 | Promotes Th2 maturation | Present in AS; its receptor, sT2, is increased in plasma in patients with more severe AS, more predictive than BNP for heart failure symptom development, and increased in patients with AS compared with AR | (84, 151) |
| TGF-β | Immunosuppressive; profibrotic; promotes Th17 maturation | ↑ in CAVD | (74) |
| IL-17RA | Receptor for IL-17; promotes Th17 maturation | Nonsignificantly increased in plasma of patients who progress to aortic valve replacement | (98) |
| IL-10 | Immunosuppressive; promotes Treg maturation | Present in CAVD; SNPs in IL10 are associated with CAVD | (8, 175) |
| IL-18 | Promotes T-cell maturation | ↑ in patients with more severe aortic stenosis | (125) |
| M-CSF | Promotes macrophage maturation | Present in CAVD | (175) |
| IL-32 | Proinflammatory | ↑ in CAVD | (171) |
CAVD, calcific aortic valve disease; Th, T helper; IL, interleukin; TNFα, tumor necrosis factor-α; CCL, C-C motif ligand; CXCL, C-X-C motif ligand; CCR, C-C receptor; IFNγ, interferon-γ; TGF-β, transforming growth factor-β; M-CSF, macrophage colony-stimulating factor; SNP, single nucleotide polymorphisms; AS, aortic stenosis; BNP, brain natriuretic peptide; AR, aortic regurgitation.