Method of treating inflammatory conditions with progesterone or progesterone analogs
a technology of progesterone and progesterone analogs, applied in the field of treating inflammatory conditions with progesterone or progesterone analogs, can solve the problems of macrophage accumulation, two billion dollars per year in the us, and the cost of disease, including productivity loss,
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example 1
Treatment of Mice with Medroxyprogesterone Acetate
[0053] The scid (severe combined immunodeficient) C.B.-17 line of mice provide an effective model of Inflammatory Bowel Disease. The disease state in these mice is triggered by the intraperitoneal injection of CD4+ T cells from a normal BALB / C mouse. The induced disease is characterized by intestinal inflammation in the large intestine, leukocytic infiltrates into the mucosa, submucosa, and mucularis, epithelial cell hyperplasia, loss of mucin-secreting cells, and ulcers with deep fissures, and diarrhea. In the mouse model, CD4+ T cells and macrophages infiltrate the bowel. The scid mouse is recognized by the art as a model for IBD. Powrie et al., Inhibition of Th1 Responses Prevents Inflammatory Bowel Disease in scid Mice Reconstituted with CD45RBhi CD4+ T Cells, Immunity 1:553-562 (1994).
[0054] 500,000 to 1×106 T cells derived from the lymph nodes of normal BALB / C mice were injected intraperitoneally into scid mice 6 weeks prior ...
example 2
Effect of Medroxyprogesterone Acetate on Macrophage TNF-α Release
[0057] The spleens of six of the mice from Example 1 were removed after the animals were sacrificed. Macrophages were isolated from the spleen of the medroxyprogesterone acetate or buffer control treated mice. TNF-α release from these macrophages was measured by ELISA following stimulation with either (1) rat anti-mouse macrophage Fc receptor antibody 2.4G2 and F(ab′)2 IgG goat anti-rat antibody, or (2) phorbol myristate acetate (“PMA”), a phorbol ester. The effect of medroxyprogesterone acetate on TNF-α release is illustrated in Table 2.
TABLE 2Effect of Medroxyprogesterone Acetate on TNF-α ReleaseTNF-αTNF-α RepeatMeasurementMeasurementMouseTreatmentStimulation(pg / ml)(pg / ml)1Buffer2.4G2 and F(ab′)2257520532IgG anti-rat187311123MPA184304231410265Buffer2.4G2 and F(ab′)2562209366MPAIgG anti-rat for 1st275630Measurement andPMA for RepeatMeasurement
[0058] Thus, these results suggest that medroxyprogesterone acetate may b...
example 3
Effect of Medroxyprogesterone Acetate on Macrophage IL-6 Release
[0059] The spleens of four of the mice from Example 1 were removed after the animals were sacrificed. Macrophages were isolated from the spleen of the medroxyprogesterone acetate or buffer control treated mice. IL-6 release from these macrophages was measured by ELISA following stimulation with rat anti-mouse macrophage Fc receptor antibody 2.4G2 and F(ab′)2 IgG goat anti-rat antibody. The effect of medroxyprogesterone acetate on IL-6 release is illustrated in Table 3.
TABLE 3Effect of Medroxyprogesterone Acetate on IL-6 ReleaseMouseTreatmentStimulationIL-6 Measurement1Buffer2.4G2 and F(ab′)2323,4062IgG anti-rat310,7503MPA298,9404266,557
[0060] Thus, these results suggest that medroxyprogesterone acetate may be inhibiting IL-6 release from macrophages, either by inhibiting its production, release, or down-regulating Fc receptors on the macrophages. Macrophages are involved in inflammatory processes, and infiltrate the ...
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