Table 1.

Effect of Therapeutic Agents in Rheumatoid Arthritis and Interstitial Lung Disease

Compound	Mechanism of Action/Targets	Effects on ILD	Effects on CS	References
GCs	Anti-inflammatory	Inhibits GM-CSF and fibrosis induced by neutrophils.	Inhibits CS-induced granulocyte aggregation.	[141–143]
Pirfenidone	TGF-β and PDGF	Acts altering the TGF-β pathway reducing fibroblast proliferation.	Indirectly acts on CS-mediated inflammation	[144–146]
Nintedanib	PDGFR, FGFR and VEGFR	Interferes with processes active in fibrosis.	Indirectly acts on CS-mediated inflammation	[146–148]
Eculizumab	C5	Inhibits C5a, a powerful chemoattractant for neutrophils.	Prevents the generation of C5a by inhibiting C5 cleavage.	[107,149]
Rituximab	Anti-CD20	Acts on lymphocytes CD20+ pulmonary infiltrates.	Reduces C3 levels	[135,150]
Tocilizumab	Interleukin-6 receptor (IL-6R)	Reduce the expression of profibrotic M2 macrophage-associated genes.	Reduces C3/C4 levels	[134,151,152]
GSH	OX-REDOX	Acts by S-glutathionylation, inflammation and cell death, involved in lung fibrosis.	Inhibits the CS-mediated damage.	[153–157]
Pentraxin	Clearance of injured tissue components and regulates related inflammation.	Inhibits differentiation of monocytes into macrophages and fibrocytes with pro-inflammatory and pro-fibrotic properties.	Inhibits C3b to prevent excessive damage.	[158,159]

Abbreviations: ILD, interstitial lung disease; CS, complement system; GCs, glucocorticoids; GM-CSF, granulocyte-macrophage colony-stimulating factor; TGF-β, transforming growth factor beta; PDGF, platelet-derived growth factor; PDGFR, platelet-derived growth factor receptor; FGFR, fibroblast growth factor receptor; VEGFR, vascular endothelial growth factor receptor; C5a, Complement 5 anaphylatoxin; IL-6R, Interleukin-6 receptor; M2, macrophages 2; GSH, Glutathione; OX-REDOX, oxidation-reduction.