. 2021 Mar 6;12(1):321–333. doi: 10.1016/j.jcmgh.2021.03.002

Table 2.

Summary of NET-targeted Therapies in IBD and Other Diseases

Targeted NET component	Inhibitors	IBD Studies	Non-IBD Studies
Peptidylarginine deiminase, a nuclear citrullinating enzyme essential for some forms of NET formation	Chloramidine, BB-Cl-amidine, neonatal inhibitory factor, streptonigrin	Chloramidine—Reduced clinical signs and symptoms in DSS-induced colitis.¹¹⁶^,¹¹⁷ Streptonigrin—Reduced colonic inflammation, weight loss, and diarrhea; improved histological scoring in DSS-induced colitis.¹¹	Murine models of lupus and MPO-ANCA–associated vasculitis.118, 119, 120
Neutrophil elastase—involved in chromatin decondensation during NET formation	Prolastin, elaspol, range of low-molecular-weight HNE inhibitors	Elaspol—Reduced weight loss and histological score in DSS-induced colitis, reduced IL-17–based inflammation¹²¹^,¹²²	Non-IBD—various including (cardio)pulmonary inflammatory diseases, RA, and cancer¹²³
NET DNA	Recombinant human DNase, DNase I	DNase I—Reduced weight loss; lower disease activity index; lower histological score; reduced thrombotic tendencies; reduced IL-1β, IL-6, and TNF-α⁶⁹^,⁷⁰	Non-IBD—good safety profile in cystic fibrosis, moderately efficacious¹²⁴
IL-1β–decorated NETs	Anakinra, rilonacept, canakinumab	Anakinra (ongoing)—IASO phase II trial for ASUC. Question: Does antagonism of IL-1 signaling in addition to intravenous corticosteroid treatment improve outcomes in ASUC patients?¹²⁵	Various including RA, FMF, and hyperimmunoglobulinemia D syndrome¹²⁶^,¹²⁷
Other approaches	- Antibody-mediated targeting of NETs for macrophage degradation.¹²⁸ Not only breaks down DNA but also proinflammatory/destructive NET proteins. - Cross-linking of NET-inhibitory receptors such as signal inhibitory receptor on leukocytes-1.¹²⁹ Inhibits NETs but preserves intracellular bacterial killing.

ANCA, antineutrophil cytoplasmic antibody; ASUC, acute severe ulcerative colitis; DSS, dextran sulfate sodium; FMF, familial Mediterranean fever; IASO, Interleukin 1 blockade in Acute Severe Colitis; IBD, inflammatory bowel disease; IL, interleukin; MPO, myeloperoxidase; NET, neutrophil extracellular trap; RA, rheumatoid arthritis; TNF-α, tumor necrosis factor alpha.