Table 1.
Cytokines as predisposing factors, diagnostic markers, and prognostic markers in venous thrombosis.
| Predisposing factor | Acute reaction and diagnostic use | Effect on thrombus resolution | |
|---|---|---|---|
| IL-1α | −899C/T ↓ SNP: 108 DVT vs. 325 controls (36) | ||
| IL-1β | rs1143634 ↓ SNP in DVT in larger cohort (4) ↔ 506 DVT vs. 1464 controls (37) IL1RN-H5H5 ↑ Leiden thrombophilia study (38) |
||
| IL-4 | −589 T allele ↑ SNP: 108 DVT vs. 325 controls (36) | ||
| IL-6 | ↔ 506 DVT vs. 1464 controls (37) −174 CC ↑ SNP: 108 VTE vs. 325 controls (36) −174 G > C ↑ SNP: 130 DVT+ and 190 DVT− (cancer patients) vs. 215 controls (39) −174 GC ↑ SNP: 119 VTE vs. 126 controls (40) −174 G > C ↔ SNP: 128 DVT, 105 PE vs. 122 controls ↔ IL6: 128 DVT, 105 PE vs. 122 controls (41) CC −572 G/C ↑ 140/246 VTE vs. 160/292 controls, respectively (42, 43) ↑IL6, 200 ovarian cancer, predictor for VTE (44) ↑IL6 in 34 VTE 322 patients with diffuse large B-cell lymphoma (45) |
−174 G > C ↔ 128 DVT, 105 PE vs. 122 controls (41) ↑ 84 VTE vs. 100 controls (46) ↑ 49 VTE vs 48 controls (47) ↑ 40 DVT+ vs. 33 DVT− (7) ↑ 201 DVT vs. 60 controls (48) ↑ abdominal cancer, post-operative [40 DVT vs. 40 non-DVT vs. 40 controls (49) ↔ 181 cases vs. 313 controls (50) ↑ 68 cases vs. 67 controls (51) |
↑ 182 recurrent VTE vs. 350 controls (52) ↑ in post-thrombotic syndrome, 49 DVT (53) ↑ in post-thrombotic syndrome, 136 DVT (mice) (54) ↑ in post-thrombotic syndrome, 387 DVT (55) ↑ risk for post-thrombotic syndrome, 110 DVT patients (56) ↑ 201 DVT vs. 60 controls (48) ↔ 181 cases vs. 313 controls (50) ↑43 DVT vs. 43 controls (57) ↑ increased risk for post-thrombotic syndrome, 803 participants SOX trial (58) |
| CXCL8/IL-8 | ↔ 506 VTE vs. 1464 controls (37) −251AT ↑ SNP: 119 VTE vs. 126 controls (40) ↑ 474 DVT vs. 474 controls (59) |
↑ 49 VTE vs. 48 controls (47) ↑ 40 DVT+ vs. 33 DVT− (7) ↔ 181 cases vs. 313 controls (50) |
↑ 182 recurrent VTE vs. 350 controls (52, 59) ↔ 181 cases vs. 313 controls (50) ↑43 DVT vs. 43 controls (57) correlation between baseline lumen diameter of the femoral thrombi and IL-8 cytokine (60) ↔ risk for post-thrombotic syndrome, 387 DVT (55) |
| IL-10 | ↓ in VTE group in trauma cohort (61) ↔ 506 VTE vs. 1464 controls (37) rs1800872 ↑ SNP IL-10 in DVT cohort (22 413 women) (4) −1082GG genotype ↓ in 660 DVT vs. 660 controls (62) ↑IL10 in 34 VTE 322 patients with diffuse large B-cell lymphoma (45) |
↓ abdominal cancer, post-operative (40 DVT vs. 40 non-DVT vs. 40 controls (49) ↔ 181 cases vs. 313 controls (50) |
↔ 181 cases vs. 313 controls (50) ↓ 43 DVT vs. 43 controls (57) ↑ increased risk for post-thrombotic syndrome, 803 participants SOX trial (58) ↔ risk for post-thrombotic syndrome, 387 DVT (55) |
| IL-12p70 | ↔ 506 VTE vs. 1464 controls (37) | ||
| IL-13 | ↑ TT genotype: 108 VTE vs. 325 controls (female) (36) | ||
| CCL2/MCP-1 | −2518AG ↑ SNP: 119 VTE vs. 126 controls (40) | ↔ 181 cases vs. 313 controls (50) | ↑ 182 recurrent VTE vs. 350 controls (52) ↑ in post-thrombotic syndrome, 136 DVT (mice) (54) ↔ 181 cases vs. 313 controls (50) ↔ risk for post-thrombotic syndrome, 387 DVT (55). |
| TNF-α | ↑ TNF-α in VTE in cancer cohort (63) ↑ TNF-α and TNFA haplotype in 15 VTE in cancer cohort 157 GI cancer and controls 157 (64) ↑−308A allele 68 patients vs. 62 controls (65) |
↔ 49 VTE vs. 48 controls (47) ↑ 201 DVT vs. 60 controls (48) ↑ 68 patients vs. 67 controls (51) |
↑43 DVT vs. 43 controls (57) |
| IFN-γ | ↑ IFN-γ enhances thrombus resolution in mice through enhanced MMP9 and VEGF expression in mice (66) | ||
| TNFSF4 | SNP ↑ (921C > T), ↓ (rs3850641) 344 DVT vs. 2269 controls (67) | ||
| NF-κB | ↑ abdominal cancer, post-operative (40 DVT vs. 40 non-DVT vs. 40 controls (49) | ||
| TGF-β1 TGF-β2 |
↔ 181 cases vs. 313 controls (50) | ↔ 181 cases vs. 313 controls (50) ↓ MATS 42 recurrent DVT vs. 84 controls (68) |
|
| PDGF | ↔ 181 cases vs. 313 controls (50) | ↔ 181 cases vs. 313 controls (50) | |
| Multiplex analysis | IL1RA, EGF, HGF CXCL5, CXCL10, and Leptin ↑21 DVT vs. 20 controls (69) IL1-α, IL1-β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8/CXCL-8, IL-10, IL-12, IL-13, IL-17, IL-22, IL1RA, CCL-3/4/5/11, CXCL-5/10/11, bFGF, G-CSF, GM-CSF, VEGF, TPO, EGF, HGF, and Leptin, IFN-γ CD40L, TNF-α ↔21 DVT vs. 20 controls (69). |
This table summarizes selected key human and animal studies of c response in venous thrombosis. Arrows indicate the following: the cytokine/genetic polymorphism coding for the cytokine is elevated/more frequent (↑), decreased/less frequent (↓), or unchanged (↔) in DVT cohorts as a predisposing factor (left column), as part of the acute reaction (middle column), or as a risk factor for post-thrombotic syndrome or recurrent DVT (right column). PTS, post thrombotic syndrome; SNP, single nucleotide polymorphism; TIMP, tissue inhibitor of metalloproteases. Control, healthy control.