IL-15 sharing the same IL-15Rα chain, the stability of fish IL-2 is independent of it whereas IL-15 and especially IL-15L depend on binding to (co-presentation with) IL-15Rα for their stability and function. This suggests that, like in mammals, fish IL-2, in contrast to fish IL-15 and IL-15L, is not relying on "in trans" presentation by its receptor alpha chain. As a free cytokine, mammalian IL-2 that is secreted by activated T cells is important for a negative feedback loop by the stimulation of regulatory T cells, the latter being the cells with the highest constitutive IL-2Rα (aka CD25) expression. Besides this negative feedback loop, mammalian IL-2 also participates in a positive feedback loop because activated T cells enhance their own IL-2Rα expression. As in mammals, fish IL-2 also stimulates T cell proliferation and appears to preferentially stimulate regulatory T cells. Fish IL-2 induces the expression of cytokines of both type 1 (Th1) and type 2 (Th2) immunity. As has been found in some studies on mammalian IL-2, data suggest that fish IL-2 can form homodimers and that this is an ancient property of the IL-2/15/15L-family cytokines. Homologues of IL-2 have not been reported for jawless fish (hagfish and lamprey) or invertebrates. Role in disease While the causes of itchiness are poorly understood, some evidence indicates that IL-2 is involved in itchy psoriasis. Medical use Pharmaceutical analogues Aldesleukin is a form of recombinant interleukin-2. It is manufactured using recombinant DNA technology and is marketed as a protein therapeutic and branded as Proleukin. It has been approved by the Food and Drug Administration (FDA) and in several European countries for the treatment of cancers (malignant melanoma, renal cell cancer) in large intermittent doses and has been extensively used in continuous doses. Interking is a recombinant IL-2 with a serine at residue 125, sold by Shenzhen Neptunus. Neoleukin 2/15 is a computationally designed mimic of IL-2 that was designed to avoid common side effects. However, clinical trials into this candidate were discontinued. Dosage Various dosages of IL-2 across the United States and across the world are used. The efficacy and side effects of different dosages is often a point of disagreement. The commercial interest in local IL-2 therapy has been very low. Because only a very low dose IL-2 is used, treatment of a patient would cost about $ 500 commercial value of the patented IL-2. The commercial return on investment is too