Table 2.

Therapeutic agents targeting monocytes/macrophages and their functional activities.

Agent	Targets	Actions	Developmental Stage	Ref.
Etanercept	TNF receptor	Blocks TNFα signaling; shifts Mos/Mφs toward an anti-inflammatory phenotype and induces apoptosis of Mos/Mφs	JIA–marketing	[61,62]
Adalimumab	TNF	Blocks TNFα signaling; shifts Mos/Mφs toward an anti-inflammatory phenotype; induces apoptosis of Mos/Mφs and reduces Mo migration into the joint	polyarticular JIA–marketing	[63,149,154]
Infliximab	TNF	Blocks TNFα signaling; shifts Mos/Mφs toward an anti-inflammatory phenotype and induces apoptosis of Mos/Mφs; increases circulating nonclassical Mos and decreases circulating classical Mos; reduces CCR2 and CXCR4 expression on the nonclassical Mo subpopulation	JIA–marketing	[62,63,64]
Certolizumab	TNF	Blocks TNFα signaling; induces HO-1 mRNA and protein production in Mos; inhibits IL-1β production at the mRNA and protein level upon LPS stimulation	polyarticular JIA–phase III	[154]
Anakinra	IL-1β receptor	Blocks IL-1β signaling	sJIA–marketing	[109]
Canakinumab	IL-1β	Blocks IL-1β signaling	sJIA–marketing	[106,107]
Rilonacept	IL-1β/IL-1α	Blocks IL-1 signaling; skews Mos toward an alternatively activated phenotype	sJIA–phase II	[155]
Tocilizumab	IL-6 receptor	Blocks IL-6 signaling; shifts Mos/Mφs toward an anti-inflammatory phenotype and induces apoptosis of Mos	sJIA/polyarticular JIA–marketing	[150,151]
Sarilumab	IL-6 receptor	Blocks IL-6 signaling	polyarticular JIA–phase II	[156]
Ustekinumab	IL-12/IL-23	Blocks IL-12/IL-23 signaling	psoriatic arthritis–marketing	[157]
Secukinumab	IL-17A	Blocks IL-17 signaling; decreases serum IL-6, S100A8, S100A9, VEGF, TNFα, osteopontin, and MMP	ERA/juvenile psoriatic arthritis –phase III	[158]
Ixekizumab	IL-17A	Blocks IL-17 signaling	ERA/juvenile psoriatic arthritis –phase III	[159]
Emapalumab	IFNγ	Blocks IFNγ signaling	sJIA–phase II	[160]
Abatacept	CTLA-4	Blocks ACPA and RF mediated cytokine production in human Mφs; modulates proinflammatory Mφ responses upon cytokine-activated T cell and TLR stimulation	Polyarticular JIA–marketing	[161,162]
Tofacitinib	JAK1/JAK3	Small molecule that abrogates TNF- induced STAT1 activation; inhibits proinflammatory mediator production	polyarticular JIA–marketing	[153]
Baricitinib	JAK1/JAK2	Decreases expression of the inflammatory IP-10 and increases IL-10 production	JIA–phase III	[163]
Upadacitinib	JAK1	Selectively targets JAK1 dependent disease drivers such as IL-6 and IFNγ	Polyarticular JIA–phase I	[164]
Mavrilimumab (CAM-3001)	GM-CSF receptor α	Blocks GM-CSF signaling and classically activated polarization	RA–phase IIb	[165]
Otilimab (MOR103)	GM-CSF	Blocks GM-CSF signaling and classically activated polarization	RA–phase III	[166]
Givinostat (ITF2357)	histone deacetylase inhibitor	Prevents LPS-induced TNFα gene transcription and secretion of IL-1β	JIA–phase II	[167]
Gamma-linolenic acid	n-6 polyunsaturated fatty acids	Inhibits inflammatory responses through inactivation of NFκB and AP-1 by suppressing oxidative stress and the ERK and JNK signal transduction pathways in LPS-induced Mφs	JIA-phase I	[168]
Sinomenine	plant alkaloid	Attenuates CD11b+F4/80+CD64+ resident Mφs in the synovial tissue and reduces number of CD14+CD16+ circulating Mos	Herbal medicine	[169]
Thapsigargin	inhibitor of SERCA	Decreases the number of TNF-induced classically activated Mφs and increases the number of alternatively activated Mφs	preclinical	[170]
Withaferin-A	steroidal lactone	Promotes classically activated Mφ to alternatively activated Mφ repolarization	preclinical	[171]
Berberine	antimicrobial agent	Increases the proportion of alternatively activated Mφs and decreases the proportion of classically activated Mφs, downregulates HIF-1α expression in synovial Mφs	Preclinical	[172]
Ramucirumab	VEGF	Blocks VEGF signaling	preclinical	[173]
Ranibizumab	VEGF	Blocks VEGF signaling	preclinical	[174]
2-benzoyl-phenoxy acetamide	benzophenone analog	Targets VEGF and HIF-1α	preclinical	[175]
Paclitaxel (PTX)	tubulin, chemotherapy	Targets VEGF and HIF-1α	preclinical	[176]
pLVX-shRNA-HIF-1α	shRNA targeting HIF-1α	Inhibits HIF-1α and VEGF expression, leading to decreased proinflammatory cytokine expression	Preclinical	[177]
Clodronate liposomes	release chlorophosphate	Mφ depletion	Preclinical	[178]
Human umbilical cord blood-derived mesenchymal stem cells	stem cells	Polarizes naive Mφs toward an alternatively activated phenotype	preclinical	[179]