Our novel topical/dermal Fenoldopam: reduced secretion of the eight cytokines by activated human T cells reduced IL‐1 β and IL‐6 secretion by human lipopolysaccharide‐inflamed skin eliminated preferentially >90% of live and large/proliferating human T cells. Next, we invented a novel topical/dermal Fenoldopam formulation, allowing it to be spread on, and providing prolonged and regulated release in, diseased skin.
Highly selective D1‐like receptor agonists, primarily Fenoldopam (Corlopam) – a D1‐like receptor agonist and a drug used in hypertension, induced the following suppressive effects on activated T cells of Psoriasis patients: reduced chemotactic migration towards the chemokine SDF‐1/ CXCL12 reduced dramatically the secretion of eight cytokines: tumor necrosis factor‐ α, interferon‐ γ, interleukin‐1 β ( IL‐1 β), IL‐2, IL‐4, IL‐6, IL‐8 and IL‐10 and reduced three T cell activation proteins/markers: CD69, CD28 and IL‐2. In line with that, 25‐fold more D1R + T cells are present in Psoriasis humanized mouse model. The skin of Psoriasis patients contains 20‐fold more D1R + T cells than healthy human skin. Interestingly, DR agonists shift the membrane potential ( V m) of both resting and activated human T cells, and induces instantaneous T cell depolarization within 15 seconds only. Thus, activation of DRs in T cells depolarize these immune cells, alike activation of DRs in neural cells. In our previous studies we found that activation of dopamine receptors (DRs) in resting human T cells activates these cells, and induces by itself many beneficial T cell functions. In this study, we found that normal human T cells express all types of DRs, and that expression of D1R, D4R and D5R increases profoundly after T cell receptor (TCR) activation.
In these pathological conditions, selective silencing of activated T cells through physiological receptors they express remains a clinical challenge. Activated T cells are pathological in various autoimmune and inflammatory diseases including Psoriasis, and also in graft rejection and graft‐versus‐host‐disease.
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