Endogenous Metabolite; immunosuppressant and anti-inflammatory agent; Glucocorticoid-receptor

在外周血单核细胞 (PBMC) 中，可的松 (2.8-28,000 nM) 剂量依赖性地减少皮质醇诱导的细胞凋亡 [1]。

在兔子中，可的松（2 mg/kg；每隔一天肌肉注射一次，持续两个月）可降低结核菌素反应和 BCG（结核分枝杆菌疫苗株）病变 [2]。

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在幼鸡中检测单剂量醋酸可的松（5或10mg/100g体重）对B细胞的影响。循环B淋巴细胞数量的剂量依赖性增加及其Ig类分布的变化之后，脾浆细胞和血清免疫球蛋白的平行增加。较高剂量的可的松引起Bmu和Bgamma细胞的变化，而较低剂量主要影响Bmu细胞。在这些类固醇诱导的变化之前，囊泡皮质区域的淋巴细胞减少，先前的囊切除术阻止了类固醇诱导的循环B淋巴细胞和组织浆细胞的增加。结果表明，可的松可以诱导法氏囊淋巴细胞从法氏囊迁移，随后在外周淋巴组织中沉淀，成为成熟的浆细胞[4]。

糖皮质激素（GC）被认为通过诱导胸腺细胞和成熟外周血淋巴细胞凋亡来调节免疫细胞系统。在这里，我们报道了皮质醇在有丝分裂原活化的外周血单核细胞（PBMC）中诱导的细胞凋亡被皮质醇的氧化代谢产物可的松抑制。PBMC中的细胞凋亡通过细胞死亡ELISA程序进行定量，该程序可以特异性检测片段化的DNA。皮质醇在刀豆球蛋白A刺激的PBMC中以大于10ng/ml（28nM）的浓度诱导PBMC凋亡，并且皮质醇在1-10000ng/ml（2.8-28000nM）浓度范围内剂量依赖性地抑制这种凋亡。泼尼松，一种合成的氧化GC，也以剂量依赖的方式抑制皮质醇的凋亡诱导作用。在来自16名健康受试者的PBMC中一致观察到可的松对皮质醇诱导的细胞凋亡的抑制。类固醇对[3H]地塞米松与PBMC结合的抑制活性的检查表明，可的松可以与细胞GC受体（GC Rs）结合，但可的松与GC Rs的亲和力为皮质醇的1/30或更低。这一结果提出了可的松在皮质醇介导的活化人PBMC细胞凋亡调控中的可能作用。可的松对皮质醇诱导的细胞凋亡的抵消作用可能部分通过GC受体（GC Rs）的干预发生，但也可能是由于与细胞GC Rs介导的途径不同的未知途径[1]。

Animal/Disease Models: Male New Zealand white rabbits (2.1-2.4 kg) were injected with BCG six days after the first dose [2]
Doses: 2 mg/kg
Route of Administration: intramuscularinjection every other day for 2 months
Experimental Results: BCG lesions and tuberculosis bacteria were diminished factor reaction. diminished the number of infiltrating mononuclear cells (MN), the number of caseous necrosis and ulcers, and the percentage of β-galactosidase-positive NMs.

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Rabbits were injected intramuscularly with cortisone acetate (2 mg/kg) on alternate days. Six days after the first injection these rabbits and controls were injected intradermally in multiple sites with BCG (the vaccine strain of tubercle bacillus). Periodically, over the next 2 months, the resulting lesions were measured and surgically biopsied, and the animals were tuberculin-tested. Macrophage activation in the BCG lesions was evaluated histochemically by staining for beta-galactosidase activity. Both BCG lesions (and tuberculin reactions) in the cortisone-treated group were considerably smaller than those in the control group. Cortisone was highly effective in reducing the number of infiltrating mononuclear cells (MN), the amount of caseous necrosis and ulceration, and the percent of NM that were beta-galactosidase-positive. The decreased activation and reduced number of macrophages readily explains the increased susceptibility to tuberculosis found amoung patients receiving glucocorticosteroids. In the BCG lesions, the local decrease in the number and function of leukocytes probably explains the decreased tissue necrosis. Such antiinflammatory effects of corticosteroids may offset, in selected antimicrobial-treated cases, the hormone's detrimental effect on host resistance to infectious agents.[2]

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Cortisone is a normal component of breastmilk that passes from the mother's bloodstream into milk and might have a role in intestinal maturation, the intestinal microbiome, growth, body composition or neurodevelopment, but adequate studies are lacking. Concentrations follow a diurnal rhythm, with the highest concentrations in the morning at about 7:00 am and the lowest concentrations in the late afternoon and evening. Cortisone has not been studied in breastmilk after exogenous administration in pharmacologic amounts. Although it is unlikely that dangerous amounts of cortisone would reach the infant, a better studied alternate drug might be preferred. Medium to large doses of corticosteroids given systemically or injected into joints or the breast have been reported to cause temporary reduction of lactation.
◉ Effects in Breastfed Infants
None reported with any corticosteroid.
◉ Effects on Lactation and Breastmilk
Published information on the effects of cortisone on serum prolactin or on lactation in nursing mothers was not found as of the revision date. Medium to large doses of corticosteroids given systemically or injected into joints or the breast have been reported to cause temporary reduction of lactation.
A study of 46 women who delivered an infant before 34 weeks of gestation found that a course of another corticosteroid (betamethasone, 2 intramuscular injections of 11.4 mg of betamethasone 24 hours apart) given between 3 and 9 days before delivery resulted in delayed lactogenesis II and lower average milk volumes during the 10 days after delivery. Milk volume was not affected if the infant was delivered less than 3 days or more than 10 days after the mother received the corticosteroid. An equivalent dosage regimen of cortisone might have the same effect.
A study of 87 pregnant women found that betamethasone given as above during pregnancy caused a premature stimulation of lactose secretion during pregnancy. Although the increase was statistically significant, the clinical importance appears to be minimal. An equivalent dosage regimen of cortisone might have the same effect.

[1]. Cortisone counteracts apoptosis-inducing effect of cortisol in human peripheral-blood mononuclear cells. Int Immunopharmacol. 2001 Nov;1(12):2109-15.

[2]. The effect of cortisone on the accumulation, activation, and necrosis of macrophages in tuberculous lesions. Inflammation. 1978 Jun;3(2):159-76.

[3]. In Vivo Antifungal Activity of Monolaurin against Candida albicans Biofilms. Biol Pharm Bull. 2018;41(8):1299-1302.

[4]. In vivo effects of cortisone on the B cell line in chickens. J Immunol. 1975 Nov;115(5):1370-4.

Cortisone is a C21-steroid that is pregn-4-ene substituted by hydroxy groups at positions 17 and 21 and oxo group at positions 3, 11 and 20. It has a role as a human metabolite and a mouse metabolite. It is a 17alpha-hydroxy steroid, a 21-hydroxy steroid, an 11-oxo steroid, a 20-oxo steroid, a C21-steroid, a 3-oxo-Delta(4) steroid, a primary alpha-hydroxy ketone, a tertiary alpha-hydroxy ketone and a glucocorticoid. It derives from a hydride of a pregnane.
A naturally occurring glucocorticoid. It has been used in replacement therapy for adrenal insufficiency and as an anti-inflammatory agent. Cortisone itself is inactive. It is converted in the liver to the active metabolite hydrocortisone. (From Martindale, The Extra Pharmacopoeia, 30th ed, p726)
Cortisone is a Corticosteroid. The mechanism of action of cortisone is as a Corticosteroid Hormone Receptor Agonist.
Cortisone has been reported in Homo sapiens with data available.
Therapeutic Cortisone is a corticosteroid with potent glucocorticoid activity. Therapeutic cortisone is the inactive precursor molecule of the active hormone cortisol, which is the hydroxylation product of cortisone by 11-beta-steroid dehydrogenase. Cortisol increases blood pressure and blood sugar levels, and suppresses the immune system, therefore cortisone is used to treat allergies or inflammation.
Cortisone is a steroid hormone synthesized and secreted by the adrenal gland and necessary for life. It is involved with maintaining cardiovascular function, blood glucose balance, regulating the inflammatory response and metabolism of proteins, carbohydrates, and fat.
A naturally occurring glucocorticoid that has been used in replacement therapy for ADRENAL INSUFFICIENCY and as an anti-inflammatory agent. Cortisone itself is inactive; it is converted in the liver to the active metabolite HYDROCORTISONE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p726)
See also: Cortisone Acetate (active moiety of).

C21H28O5

360.45

360.193

C, 69.98; H, 7.83; O, 22.19

53-06-5

Cortisone acetate;50-04-4;Cortisone-d8;Cortisone-13C3;2350278-95-2;Cortisone-d7;1261254-36-7;Cortisone-d2;2687960-86-5

222786

Typically exists as off-white to light yellow solids at room temperature

1.3±0.1 g/cm3

567.8±50.0 °C at 760 mmHg

223-228 °C (dec.)(lit.)

311.2±26.6 °C

0.0±3.5 mmHg at 25°C

1.587

1.44

91.67

2

5

2

26

724

6

C[C@@]1(C2)[C@](C(CO)=O)(O)CC[C@@]1([H])[C@]3([H])CCC4=CC(CC[C@]4(C)[C@@]3([H])C2=O)=O

MFYSYFVPBJMHGN-ZPOLXVRWSA-N

InChI=1S/C21H28O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h9,14-15,18,22,26H,3-8,10-11H2,1-2H3/t14-,15-,18+,19-,20-,21-/m0/s1

Pregn-4-ene-3,11,20-trione, 17,21-dihydroxy

NSC 9703; NSC9703; NSC-9703; 17-Hydroxy-11-dehydrocorticosterone; Kendall's compound E; 53-06-5; Cortisate; Cortistal; Cortivite; Andreson; Cortisal;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~277.44 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (6.94 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (6.94 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (6.94 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。