Table 1.
Cytokines and chemokines associated with pulmonary vascular inflammation.
| Cytokines/Chemokines | Reference | Cellular Source | Targeted Cells | Function in HPH |
|---|---|---|---|---|
| IL-1α | (100) | PAECs PASMCs |
PASMCs | Enhancement of IL-1β expression Promotion of PASMC proliferation |
| IL-1β | (101–104) | Monocytes/macrophages PAECs PASMCs Fibroblasts Lymphocytes |
Macrophages PASMCs |
Recruitment of macrophages Promotion of PASMC proliferation and anti-apoptosis Induction of pyroptosis |
| IL-6 | (105–113) | Monocytes/macrophages PAECs PASMCs Fibroblasts T- and B-cells |
Lymphocytes Th17 Macrophages PAECS PASMCs |
Promotion of PAEC proliferation and of PASMC apoptosis resistance Recruitment of lymphocytes Differentiation of Th17 Polarization of macrophages Downregulation of BMPR-II |
| IL-10 | (114, 115) | TH1- and TH2-cells CTLs B-cells MCs Macrophages |
Macrophages PASMCs |
Reduction of macrophage infiltration Decrease expression of TGF-β and IL-6 Inhibition of excessive PASMC proliferation |
| IL-17 | (83, 116, 117) | Th17 | Th17& Tregs PAECs |
Imbalance of the Th17/Treg ratio Promotion of PAEC proliferation Angiogenesis |
| IL-18 | (101, 104) | Macrophages DCs |
Macrophages PASMCs |
Functions synergistically with IL-1β |
| IL-33 | (118) | PAECs Fibroblasts |
PAECs | Enhances proliferation, adhesion and spontaneous angiogenesis of PAECs |
| TNF-α | (119–121) | Many cells including monocytes/macrophages, PAECs | PASMCs | Promotion of GM-CSF secretion Promotion of the proliferation of PAECs and PASMCs Repression of BMPR-II in PAECs and PASMCs |
| TRAIL | (122–124) | Monocytes/macrophages | PASMCs | Promotion of PASMC proliferation Activation of NF-κB signaling |
| TGF-β | (125–131) | PASMCs, fibroblasts, monocytes, some T cells, B-cells, | PAECs PASMCs |
Proliferation of PASMCs Deposition of extracellular matrix EndMT Dysregulation of TGF-β and BMP signaling pathways |
| MIF | (132–135) | Macrophages, lymphocytes, ECs, SMCs, and epithelial cells | PAECs PASMCs Fibroblasts |
Hyperproliferation of PAECs, PASMCs and, fibroblasts Vasoconstriction |
| HIMF | (136–140) | Alveolar epithelium Fibroblasts |
PASMCs PAECs Macrophages |
Induction of inflammatory mediator production Proliferation of PASMCs and PAECs Mediates HMGB1/RAGE signaling Activation of HIF and NF-κB signaling Warburg effect |
| HMGB1 | (69, 141, 142) | Necrotic PAECs, PASMCs and innate immune cells | PASMCs | Enhancement of the expression of IL-6 Downregulation of BMPR-II Promotion of proliferation and migration of PASMCs |
| CCL2/MCP-1 | (25, 143–145) | PAECs PASMCs |
monocytes/macrophages PASMCs Fibroblasts |
Chemotactic monocytes/macrophages Activation of PASMCs and fibroblasts |
| CCL5/RANTES | (35, 146, 147) | T cells, PAECs, PASMCs, macrophages, fibroblasts, epithelial cells | monocyte/macrophage PASMCs PAECs |
Pro-inflammatory Enhancement of monocyte/macrophage adhesion to PAECs and macrophage infiltration Induction of pulmonary angiogenesis and occlusion Promotion proliferation and migration of PASMCs |
| CXCL9 | (148, 149) | Monocytes | PAECs | Induction of PAEC apoptosis |
| CXCL10 | (148, 149) | Monocytes | PAECs | Induction of PAEC apoptosis |
| CXCL12 | (150–153) | Bone marrow stromal cells, fibroblasts | PASMCs | Promotion of PASMC proliferation and interference with cell cycle progression |
| CX3CL1/Fractalkine | (25, 33, 154) | PAECs, DCs, macrophages, T cells, SMCs | Monocytes/macrophages γδ T cells DCs Pericytes PASMCs |
Stimulation of leukocyte capture, chemotaxis and transport Monocyte recruitment Macrophage polarization Promotion of proliferation in pericytes and PASMCs |