Interleukins are a group of cytokines (secreted proteins and signaling molecules) that were first seen to be expressed by white blood cells (leukocytes). The function of the immune system depends in a large part on interleukins, and rare deficiencies of a number of them have been described, all featuring autoimmune diseases or immune deficiency. The majority of interleukins are synthesized by helper CD4 T lymphocytes, as well as through monocytes, macrophages, and endothelial cells. They promote the development and differentiation of T and B lymphocytes, and hematopoietic cells. Interleukin receptors on astrocytes in the hippocampus are also known to be involved in the development of spatial memories in mice.
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LMT-28 (LMT28) is a specific blocker of IL-6 signaling via inhibits IL-6Rβ (gp130) with IC50 of 5.9 uM (IL-6–induced luciferase activity), selectively inhibits IL-6–induced phosphorylation of STAT3, JAK2, and gp130; does not affect LIF-induced STAT3 activation and not inhibit IL-11 stimulation on HepG2 cells; binds directly and specifically to gp130, and thereby inhibits the interaction of gp130 with the IL-6/IL-6Rα complex; inhibits IL-6–induced proliferation of the human erythroleukemic cell line TF-1 with IC50 of 7.5 uM; inhibits IL-6–induced TNF-α production, ameliorates the progression of pancreatitis in mice.
A potent IL-5 receptor antagonist that inhibits the binding of IL-5 to its receptor on peripheral human eosinophils and butyric acid-treated eosinophilic HL-60 clone 15 cells with IC50 of 1.0 and 0.57 uM, respectively; inhibits IL-5-prolonged eosinophil survival with IC50 of 0.45 uM and does not affect the GM-CSF-prolonged eosinophil survival; inhibits antigen-induced infiltration of eosinophils and lymphocytes into the bronchoalveolar lavage fluid (BALF) in BN rats (EC50=0.32 mg/kg and 0.12 mg/kg, respectively).
SP 4206 is a high-affinity (Kd=70 nM) small molecule that blocks blocks the binding of the IL-2α receptor (IL-2Rα) to IL-2; targets virtually the same critical "hot-spot" residues on IL-2 that drive binding of IL-2Rα.
Suplatast tosilate is a cytokine inhibitor that attenuates IL-2, IL-5 and IL-13 production and has no effect on IFN-γ production; suppresses IgE production, eosinophil infiltration and histamine release; exhibits antiasthmatic, anti-inflammatory and antifibrotic activity in vivo and is orally active.
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