In the case of local IL-2 application, the therapeutic window spans several orders of magnitude.Some common side effects:
flu-like symptoms (fever, headache, muscle and joint pain, fatigue)
nausea/vomiting
dry, itchy skin or rash
weakness or shortness of breath
diarrhea
low blood pressure
drowsiness or confusion
loss of appetiteMore serious and dangerous side effects sometimes are seen, such as breathing problems, serious infections, seizures, allergic reactions, heart problems, kidney failure or a variety of other possible complications. The most common adverse effect of high-dose IL-2 therapy is vascular leak syndrome (VLS; also termed capillary leak syndrome). It is caused by lung endothelial cells expressing high-affinity IL-2R. These cells, as a result of IL-2 binding, causes increased vascular permeability. Thus, intravascular fluid extravasate into organs, predominantly lungs, which leads to life-threatening pulmonary or brain oedema.Other drawbacks of IL-2 cancer immunotherapy are its short half-life in circulation and its ability to predominantly expand regulatory T cells at high doses.Intralesional IL-2 used to treat in-transit melanoma metastases is generally well tolerated. This is also the case for intralesional IL-2 in other forms of cancer, like nasopharyngeal carcinoma. Pharmaceutical derivative
Eisai markets a drug called denileukin diftitox (trade name Ontak), which is a recombinant fusion protein of the human IL-2 ligand and the diphtheria toxin. This drug binds to IL-2 receptors and introduces the diphtheria toxin into cells that express those receptors, killing the cells. In some leukemias and lymphomas, malignant cells express the IL-2 receptor, so denileukin diftitox can kill them.
The main mechanism of this phenomenon in vivo is due to the prolongation of the cytokine half-life in circulation. Depending on the clone of IL-2 mAb, IL-2 ic  can selectively stimulate either CD25high (IL-2/JES6-1 complexes), or CD122high cells (IL-2/S4B6). IL-2/S4B6 immune complexes have high stimulatory activity for NK cells and memory CD8+ T cells and they could thus replace the conventional IL-2 in cancer immunotherapy. On the other hand, IL-2/JES6-1 highly selectively stimulate regulatory T cells and they could be potentially useful for transplantations and in treatment of autoimmune diseases. History
According to an immunology textbook: "IL-2 is particularly important historically, as it is the first type I cytokine that was cloned, the first type I cytokine for which a receptor component was cloned, and was the first short-chain type I cytokine whose receptor structure was solved. Many general principles have been derived from studies of this cytokine including its being the first cytokine demonstrated to act in a growth factor–like fashion through specific high-affinity receptors, analogous to the growth factors being studied by endocrinologists and biochemists". : 712 In the mid-1960s, studies reported "activities" in leukocyte-conditioned media that promoted lymphocyte proliferation. : 16  In the mid-1970s, it was discovered that T-cells could be selectively proliferated when normal human bone marrow cells were cultured in conditioned medium obtained from phytohemagglutinin-stimulated normal human lymphocytes. : 712  The key factor was isolated from cultured mouse cells in 1979 and from cultured human cells in 1980. The gene for human IL-2 was cloned in 1982 after an intense competition.