INTENDED USE

This Human Interleukin 2 ELISA Kit is to be used for the in vitro quantitative determination of human interleukin 2 (IL-2) concentrations in serum, plasma, cell culture supernatant, and other biological fluids. This kit is intended FOR LABORATORY RESEARCH USE ONLY and is not for use in diagnostic or therapeutic procedures.

INTRODUCTION

Interleukin 2 (IL-2) is a lymphokine synthesized and secreted primarily by T helper lymphocytes that have been activated by stimulation with certain mitogens or by interaction of the T cell receptor complex with antigen/MHC complexes on the surfaces of antigen-presenting cells. The response of T helper cells to activation is induction of the expression of IL-2 and receptors for IL-2 and, subsequently, clonal expansion of antigen-specific T cells. At this level IL-2 is an autocrine factor, driving the expansion of the antigen-specific cells. IL-2 also acts as a paracrine factor, influencing the activity of other cells, both within the immune system and outside of it. B cells and natural killer (NK) cells respond to IL-2 when properly activated. The so-called lymphocyte activated killer, or LAK cells, appears to be derived from NK cells under the influence of IL-2.

Human IL-2 is a glycoprotein with an apparent molecular weight of 15,000 - 18,000. Natural IL-2 is glycosylated and varying degrees of glycosylation apparently account for the observed range of molecular weights seen on SDS-PAGE. Human IL-2 is synthesized as a polypeptide of 153 amino acid residues. The first 20 amino acids represent a signal sequence that is cleaved to produce the mature factor. The mature protein contains three cysteine residues, two of which form a disulfide bond that is required for biological activity. Murine IL-2 is approximately 63% identical to human IL-2, but contains a unique stretch of repeated glutamine residues. There is marked species cross-reactivity as human IL-2 has been found to be active on murine cell lines. Cells known to produce IL-2 include thymocytes, gamma delta T cells, B cells, CD4+ and CD8+ T cells, and neurons plus astrocytes.

IL-2 is a factor produced and secreted primarily by activated T helper cells that acts as a autocrine factor driving the expansion of antigen-specific cells and as a paracrine factor influencing the activity of a number of other cells including B cells, NK cells and LAK cells. A simplified but useful view of these activities is of lymphocytes expanding under the influence of IL-2 and becoming the target of other cytokines that cause their functional differentiation.

With respect to the specific role of IL-2 on the differentiation of T cells, the separation of CD4+ T helper cells into the categories of TH1 and TH2 according to their function in cell mediated or humoral immunity is a concept that is proving useful. In this system each category of cells secretes a characteristic set of cytokines that functions as a network to push the system either towards cellular immunity (delayed type hyper-sensitivity and cellular cytotoxicity) associated with TH1, or towards humoral immunity (antibody-mediated) associated with TH2. IL-2, along with IFN-gamma and TNF-beta, is a defining product of the TH1 subset. Although the TH1 and TH2 subsets are relatively clearly defined in the murine immune system, these categories are not so clear-cut in the human immune system where the designations TH1-like and TH2-like have been suggested.

Other cells under the possible influence of IL-2 are neutrophils, monocytes, and gamma delta T cells, all of which demonstrate either activation, augmented function, or increased survival when exposed to IL-2. Finally, it should be mentioned that IL-2 is finding its way, along with many other cytokines, into the neurosciences as a possible neuromodulator and growth regulator of glial cells.

Because of the central role of the IL-2/IL-2R system in mediation of the immune response, it is obvious that monitoring and manipulation of this system has important diagnostic and therapeutic implications. IL-2 has shown promise as an anti-cancer drug by virtue of its ability to stimulate the proliferation and activities of tumor-attacking LAK and TIL (tumor-infiltrating lymphocytes) cells. However, problems with IL-2 toxicity are still of concern and merit investigation.

This IL-2 ELISA is a ready-to-use 4.5-hour solid phase immunoassay readily capable of measuring IL-2 levels in serum, plasma, cell culture supernatant, and other biological fluids in the range of 0 to 2500 pg/mL. This assay has shown no cross-reactivity with other cytokines tested, and is expected to be used effectively for further investigations into the relationship between IL-2 and the various conditions mentioned.

CITATIONS

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