IL-15 acting through IL-15 receptors (including high-affinity IL-15R alpha chain) is a key cytokine influencing the development of natural killer cells in bone marrow, and proliferation and maintenance of the memory CD3+ cell pool.
IL-15 acting through IL-15 receptors (including the high-affinity IL-15R alpha chain) is a key cytokine influencing the development of natural killer cells in bone marrow, and proliferation and maintenance of the memory T-cell pool.
Various new longer acting IL-1 inhibitors are also proving to be very effective [ 57] and early safety and efficacy data look encouraging [ 58].
Recently, JAK1/2 inhibitor acting on IL-6-induced STAT3 phosphorylation demonstrated clinical activity in RA [ 36].
This suggests that these cytokines, in particular, may have an important role in the neurotoxic events downstream of A β. IL-17 belongs to the same cytokine subfamily as IL-6, acting to induce IL-6 expression in astrocytes.
66, 67 Inhibition of IL-23, acting upstream from IL-17, has been also studied, both in animals and in clinical studies.
49 IL-17A also stimulates keratinocytes to express IL-36 that, by acting synergistically with IL-17A, promotes expression of the antimicrobial peptides CXCL8, IL-6, and TNF-α.
The emergence of IL-17-producing and IL-22-producing T cells is differentially regulated, with ligands of the aryl hydrocarbon receptor favouring IL-22 expression and with prostaglandin E2 acting synergistically with IL-23 to favour IL-17 expression [ 35].
It also appears that centrally-acting IL-6 plays a role in the regulation of appetite, energy expenditure, and body composition [5], [28].
Unlike anakinra, which requires daily dosing, rilonacept is a longer-acting IL-1 blocker and is administered once a week.
The objective of the present study was to determine the effect of a long-acting IL-1 receptor inhibitor, AMG 108, in a double-blind, placebo-controlled, parallel-dosing study in patients with active RA who were receiving stable methotrexate (15 to 25 mg/week).
