Disease relevance of IL2

• Given these distribution characteristics and their well-documented safety profile, ALVAC- or NYVAC-based recombinants expressing feline or human IL2, respectively, were administered to domestic cats, in order to prevent the recurrence of spontaneous fibrosarcomas [1].
• Local immunotherapy of spontaneous feline fibrosarcomas using recombinant poxviruses expressing interleukin 2 (IL2) [1].
• Functional interleukin-2 receptors are expressed on natural killer-like leukemic cells from a dog with cutaneous lymphoma [2].
• The severe side effects usually associated with classical lymphokine-activated killer therapy in association with high doses of interleukin 2, such as "capillary leak syndrome," were absent in this study [3].
• Three of 20 dogs experienced partial or complete regression of lung metastases after infusion of IL-2 LDCs [4].

High impact information on IL2

• In the present study, we introduced several mutations or deletions into the signal-anchor region of the chimeric proteins in which the amino-terminal regions of two forms of cytochrome P-450 were fused to the mature portion of interleukin 2 [5].
• We identified a dog with large granular lymphocytic leukemia and cutaneous lymphoma that exhibited constitutive expression of interleukin-2 (IL-2) receptors by the leukemic peripheral blood lymphocytes [2].
• The leukemic cells phenotypically resembled natural killer (NK) cells, and their surface IL-2 receptors were functional, as determined by the capacity to bind human recombinant IL-2 with high-affinity resulting in the transduction of proliferation signals and in the development of lymphokine-activated killer cell activity [2].
• Transforming growth factor-beta was inhibitory, but tamoxifen, interleukin-1 and interleukin-2 had no effect [6].
• Phase I study of liposome-DNA complexes encoding the interleukin-2 gene in dogs with osteosarcoma lung metastases [4].

Chemical compound and disease context of IL2

• No allergic reactions were associated with inhaled IL-2 liposome therapy [7].
• An assay for the measurement of interleukin-1 (IL-1), based on its ability to induce interleukin-2 (IL-2) production by the EL-4 mouse thymoma line in the presence of the calcium ionophore A23187, was examined [8].

Biological context of IL2

• Here we report the nucleotide sequence of the canine interleukin-2 (IL-2)-encoding cDNA [9].
• The latter was significantly correlated to up-regulation of IL-2, TNF-alpha, IFN-gamma and iNOS mRNA expression [10].
• The BAL leukocyte cell count was increased significantly after inhalation of IL-2 liposomes versus inhalation of free IL-2 (P = 0.011) [11].
• Twenty dogs with chemotherapy-resistant osteosarcoma metastases to the lungs received a series of intravenous infusions of cationic liposomes and plasmid DNA encoding the canine interleukin-2 (IL-2) cDNA [4].
• Feline panleukopenia virus (FPLV) was shown to induce apoptosis to feline lymphoid cells and to reduce the expression of interleukin-2 receptor alpha on the cells [12].

Anatomical context of IL2

• Interleukin 2 (IL2) is a lymphokine which stimulates the growth of T lymphocytes [13].
• Translocation occurs only during translation, but wheat germ extracts translate IL2 mRNA whether microsomes are present or not [13].
• Surprisingly, reticulocyte lysates do not readily translate IL2 mRNA, and strongly inhibit its translation in wheat germ extracts [13].
• Although IL2 mRNA is translated into biologically active IL2 relatively efficiently in microinjected Xenopus laevis oocytes, it has been difficult to establish reproducible cell-free translation systems for this lymphokine [13].
• In this paper, we show that a wheat germ extract will translate IL2 mRNA into biologically active murine IL2, most of which is translocated into dog pancreas microsomes when these are present [13].

Associations of IL2 with chemical compounds

• IL-2 liposomes given at 0.5 x 10(6) BRMP units twice daily to dogs resulted in significantly increased BAL effector activation compared with IL-2 liposomes given at 1.0 x 10(6) BRMP units once daily (P = 0.018) and empty liposome controls (P = 0.016) [11].
• Marked elevation was found of TNF, IFN-gamma, IL-2, and IL-2R in BALF obtained from the grafted lungs in group 1 and group 2 dogs [14].
• Cyclosporine, known to interfere with IL-2 release and responses, completely blocked both ConA- and PMA-induced lymphocyte proliferation but did not interfere with ConA-triggered cluster formation [15].
• The DTH response to phytohemagglutinin (PHA) and vaccine was heightened in beta-carotene-supplemented dogs. beta-Carotene feeding did not influence mitogen-induced lymphocyte proliferation or IL-2 production [16].
• After completion of the initial course, patients were discharged from the hospital and continued on a modified regimen for outpatient therapy: IL-2, 2.0 to 2.1 x 10(6) JRU and 5-FU 250 mg twice weekly; MMC 4 mg once weekly [17].

Other interactions of IL2

• Furthermore, the expression of interleukin- (IL-2), IL-12(p40), tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-10 and transforming growth factor-beta (TGF-beta) as well as inducible nitric oxid synthase (iNOS) mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR) [10].

Analytical, diagnostic and therapeutic context of IL2

• These include interference with production of interleukin 2 (IL-2) and other lymphokines, lack of myelotoxicity and the induction of transplantation tolerance following administration of short courses to allografted rats [18].
• Further, this case illustrates the potential for the use of hematopoietic malignancies in the dog as a suitable animal model for immune targeting of IL-2 receptors as a novel treatment approach for similar malignancies of human beings [2].
• Cytokine interleukin-2, tumor necrosis factor-alpha, and interferon-gamma release after ischemia/reperfusion injury in a novel lung autograft animal model [19].
• BAL effector populations included a greater proportion and total number of lymphocytes and eosinophils after treatment with IL-2 liposomes [11].
• Evidence of intragraft interleukin-2-activated killer cells and allospecific cytolytic T lymphocytes in rejecting lung allografts [20].

References