Second, high‐affinity HMGB1 antagonists—including recombinant A‐box and glycyrrhizin—competitively bind to RAGE/TLR4, selectively inhibiting pathological inflammation while sparing physiological immunity in models of inflammatory bowel disease (IBD), experimental orchitis, Parkinson's disease, and islet transplantation, thereby exhibiting enhanced safety [206, 207, 208]. Here, TLR4 is linked to inflammatory bowel disease.