Table 8 Pharmacotherapy for IPF: agents in current clinical trials
Agent | Target | Rationale |
|---|---|---|
Pirfenidone | TGF-β, PDGF | Down-regulation of TGF-β-stimulated collagen synthesis and extracellular matrix accumulation and PDGF proliferative effects on fibroblasts |
Tyrosine kinase inhibitors | Tyrosine kinase receptors | Inhibit fibrinogenic pathways by inhibiting receptor tyrosine kinase (RTK) binding by ligands (e.g. TGF-β, PDGF-B, CTGF, FGF, VEGF) |
N-acetylcysteine | ROI (oxidant-antioxidant imbalance) | Replenish pulmonary glutathione stores and thereby antagonize signaling and tissue damaging effects of oxygen radicals (e.g. stimulatory effects of ROI on myofibroblasts) |
Anti-TGF-β | TGF-β | Block TGF-β-induced fibroblast migration & proliferation, differentiation of myofibroblasts into fibroblasts, epithelial-mesenchymal transition, and resistance of myofibroblasts to apoptosis |
Anti-CTGF | CTGF | Suppress fibroblast stimulation by CTGF |
Anti-IL-13 | IL-13 | Inhibit induction of profibrotic cytokines (e.g. TGF-β, PDGF, IGF-1, PDGF, MMP-9) |
Anti-LPA | Lysophosphatidic acid (LPA) | Prevent fibroblast recruitment into lung interstitium that can occur via the G protein-coupled LPA1 receptor |
Anti-CCL2 | CCL-2 | Inhibit cell (e.g. lymphocytes, monocytes, fibrocytes) chemotaxis/influx to lung tissue and TGF-β expression |
Anti-LOXL2 | Lysyl oxidase-like protein-2 (LOXL-2) | Inhibit LOXL2-mediated fibroblast activation and deposition/accumulation of collagen |
Plasma exchange, rituximab, steroids | Immune/inflammatory mediators | Suppress inflammation associated with an episode of acute exacerbation of IPF |