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Interleukin-2 induction, response and therapy on murine lupus lesions in the MRL/l strain
Abstract:
MRL/Mp-lpr/lpr (MRL/l) mice are widely known as poor inducers of interleukin-2 (IL-2) and low responders to IL-2. It was reconfirmed that the spleen cells of MRL/l mice induced a small amount of IL-2 in vitro. In vivo experiments revealed that recombinant IL-2 (rIL-2) affected T cell subpopulations in MRL/l mice. rIL-2 decreased the numbers of Thy-1 and Lyt-1 positive cells and increased those of Lyt-23, Lyt-123 and Lyt-null cells in the thymus. It decreased the number of T cell subpopulations in the lymph nodes and spleen. These data disclosed that IL-2 might affect not only the development of T cells but also the movement of T cells among the immune organs. Some synthetic immunomodulators augmented and others suppressed or had no effect on IL-2 induction activity in the spleen of MRL/l mice. There was no correlation between the clinical efficacy of drugs on rheumatic disease and experimental IL-2 induction activity. rIL-2 and human peripheral T cell derived IL-2 (hIL-2) produced similar results in short term therapeutic experiments. When rIL-2 (1,000 U/mouse) or hIL-2 (equivalent dose) was given to MRL/l mice intraperitoneally, once a week, from 8 to 16 weeks of age, anti-double stranded DNA (dsDNA) antibody and anti-single stranded DNA (ssDNA) antibody titers had no changes. IL-2 had no effect on the renal lesions histopathologically. IL-2 induction activity was also assayed using spleen cells of the animals at the time of necropsy. The results showed that the mice treated with IL-2 had lower IL-2 induction activity than nontreated MRL/l mice. mice, an animal model for systemic lupus