HUMAN IL-2

Uses

Antineoplastic; biological response modifier; immunostimulant.

Uses

IL-2 (interleukin 2) human has been used for the stimulation of human primary naive T lymphocytes to study the effect of microRNA-146a on IL-2 activation-induced cell death.

Uses

• IL-2 (interleukin 2) human has been used for the detection of IL-2 using 4-Fluoro-3-nitrophenyl grafted gold electrode based platform.
• It has been used for the production of tumor-specific cytotoxic T lymphocytes.
• It has been used for the proliferation of T lymphocytes.

Indications

Aldesleukin (IL-2, Proleukin) is a human recombinant interleukin-2 protein. Its antitumor action is thought to include multiple effects on the immune system, such as enhancement of T-lymphocyte cytotoxicity, induction of natural killer cell activity, and induction of interferon-γ production. Aldesleukin has been used alone and in combination with lymphokine activated killer (LAK) cells or tumor-infiltrating lymphocytes (TIL).
The drug produces remissions in 15% of patients with renal cell carcinoma, with median durations of remission of 18 to 24 months.

brand name

Proleukin (Chiron).

General Description

Aldesleukin, interleukin-2 (Proleukin),is an rDNA-derived lymphokine that differs structurallyfrom native interleukin-2 (IL-2) but has biological activitysimilar to that of the natural lymphokine. Natural IL-2 isproduced primarily by the peripheral blood lymphocytesand contains 133 amino acid residues. The immunoregulatoryeffects of aldesleukin include enhancing mitogenesis oflymphocytes, stimulating the growth of IL-2–dependentcell lines, enhancing cytotoxicity of lymphocytes, inducinglymphokine-activated killer (LAK) cells and NK cells, andinducing interferon- production. The exact mechanism ofthe antitumor activity of aldesleukin in humans is unknown.The primary indication for aldesleukin is in the treatmentof adult metastatic renal carcinoma.

General Description

Aldesleukin, T-cell growth factor, thymocyte-stimulatingfactor, Proleukin, is recombinant IL-2 expressed in an engineeredstrain of E. coli containing an analog of the humanIL-2 gene.Aldesleukin enhances lymphocyte mitogenesis and stimulateslong-term growth of human IL-2-dependent cell lines.
IL-2 also enhances the cytotoxicity of lymphocytes. Inductionof NK cell and lymphocyte-activated killer (LAK) cell activityoccurs, as does induction of production. In mouse andhuman tumor cell lines, aldesleukin activates cellular immunityin patients with profound lymphocytosis, eosinophilia,and thrombocytopenia. Aldesleukin also activates the productionof cytokines, including tumor necrosis factor (TNF),IL-1, and IFN-γ. In vivo experiments in mouse tumor modelshave shown inhibition of tumor growth. The mechanism ofthe antitumor effect of aldesleukin is unknown.
Aldesleukin is indicated for the treatment of metastaticrenal cell carcinoma in adults. It is also indicated for thetreatment of metastatic melanoma in adults. Research isunder way on the use of aldesleukin for the treatment of variouscancers (including head and neck cancers), treatment ofacute myelogenous leukemia, and adjunct therapy in thetreatment of Kaposi sarcoma. Renal and hepatic function istypically impaired during therapy with aldesleukin, so interactionwith other drugs that undergo elimination by these organsis possible.

Biochem/physiol Actions

Interleukin-2 (IL-2) is an immunomodulatory factor produced by certain subsets of T lymphocytes. This lymphokine promotes long-term growth of activated T cells and related cell types. IL-2 plays a role in the activation and proliferation of natural killer cells, induces γ-interferon and B cell growth factor secretion, and modulates the expression of the IL-2 receptor. IL-2 expression is known to reduce with age and results in influenza infection, neoplasms and lethal autoimmunity. IL-2 participates in T cell proliferation and differentiation and controls the homeostasis of T cell. As a part of immune response, IL-2 stimulates the action of T helper cell 1 and 2 along with endothelial white blood cells of skeletal muscles. IL-2 regulation is controlled by c-rel protein. IL-2 is a neurotrophic molecule and has special functions in cortical, hippocampal, septal, cerebellar and retinal neurons.

Clinical Use

Recombinant interleukin-2
Treatment of metastatic renal cell carcinoma

Side effects

Several serious toxicities have been observed, with a fatality rate of 5% in the initial studies. The major adverse effect is severe hypotension in as many as 85% of patients, which may lead to myocardial infarctions, pulmonary edema, and strokes.This hypotension is thought to be due to a capillary leak syndrome resulting from extravasation of plasma proteins and fluid into extravascular space and a loss of vascular tone. Patients with significant cardiac, pulmonary, renal, hepatic, or CNS conditions should not receive therapy with aldesleukin. Other adverse reactions include nausea and vomiting, diarrhea, stomatitis, anorexia, altered mental status, fevers, and fatigue.

Drug interactions

Potentially hazardous interactions with other drugs
Corticosteroids: avoid concomitant use.
Cytotoxics: avoid concomitant use with cisplatin, dacarbazine and vinblastine.

Metabolism

Greater than 80% of aldesleukin distributed to plasma, cleared from the circulation and presented to the kidney is metabolised to amino acids in the cells lining the proximal convoluted tubules. A secondary elimination pathway is IL-2 receptor- mediated uptake.