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

In peripheral blood mononuclear cells (PBMC), cortisone (2.8-28,000 nM) dose-dependently reduces cortisol-induced apoptosis [1].

In rabbits, cortisone (2 mg/kg; intramuscular every other day for two months) decreases tuberculin responses and BCG (Mycobacterium tuberculosis vaccine strain) lesions [2].

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The effects of a single dose of cortisone acetate (5 or 10 mg/100 g body weight) on B cells were examined in young chickens. A dose-dependent increase in numbers of circulating B lymphocytes and a change in their Ig-class distribution were followed by parallel increase in splenic plasma cells and serum immunoglobulins. The higher dose of cortisone produced changes in Bmu and Bgamma cells, whereas the lower dose primarily affected Bmu cells. These steroid-induced changes were preceded by lymphocyte depletion in the cortical regions of bursal follicles, and prior bursectomy prevented steroid-induced increases in circulating B lymphocytes and tissue plasma cells. The results suggest that cortisone can induce bursal lymphocytes to migrate from the bursa and to settle subsequently in peripheral lymphoid tissues where they become mature plasma cells[4].

Glucocorticoids (GCs) have been considered to regulate immune cell systems through induction of apoptosis in thymocytes and mature peripheral-blood lymphocytes. Here we report that apoptosis induced by cortisol in mitogen-activated peripheral-blood mononuclear cells (PBMC) is suppressed by cortisone, an oxidized metabolite of cortisol. Apoptosis in PBMCs is quantified by a cell death ELISA procedure, which can specifically detect fragmented DNA. Cortisol induced PBMC-apoptosis at concentrations more than 10 ng/ml (28 nM) in concanavalin A-stimulated PBMCs and cortisone suppressed this apoptosis at a concentration range of 1-10,000 ng/ml (2.8-28,000 nM) dose-dependently. Prednisone, a synthetic oxidized-GC, also suppressed the apoptosis-inducing effect of cortisol in a dose-dependent manner. Suppression of cortisol-induced apoptosis by cortisone was consistently observed in PBMCs derived from 16 healthy subjects. Examination for inhibitory activities of the steroids against [3H]dexamethasone binding to PBMCs suggested that cortisone can bind cellular GC-receptors (GC-Rs), but the affinity of cortisone to GCRs is 1/30 or less than that of cortisol. The results raised a possible role of cortisone in cortisol-mediated regulation of apoptosis in activated human PBMCs. The counteracting action of cortisone against cortisol-induced apoptosis may take place partially through intervention of GC-receptors (GC-Rs), but may also be due to unknown pathway(s) different from those mediated by cellular GC-Rs[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]

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All mice were immunosuppressed prior to oral fungal infection by administration of subcutaneous injections of Cortisone acetate (225 mg/kg). Immunosuppression was maintained throughout the experiment by administering cortisone acetate injections every other day. [3]

Effects During Pregnancy and Lactation
◉ Overview of Medications Used During Lactation
Cortisol is a normal component of breast milk. It enters breast milk from the mother's bloodstream and may play a role in intestinal maturation, gut microbiota, growth, body composition, or neurodevelopment, but sufficient research is currently lacking. Cortisol concentrations exhibit a diurnal rhythm, peaking around 7 AM and reaching their lowest levels in the late afternoon and evening. The distribution of exogenously administered pharmacological doses of cortisol in breast milk has not been studied. While it is unlikely that infants will ingest dangerous doses of cortisol, more well-studied alternative medications should perhaps be prioritized. Moderate to high doses of corticosteroids administered systemically or injected into joints or the breast have been reported to cause a temporary decrease in lactation.
◉ Effects on Breastfed Infants
There are currently no reports related to corticosteroids.
◉ Effects on Lactation and Breast Milk
As of the revision date, no published information has been found regarding the effects of cortisone on serum prolactin or lactation in breastfeeding mothers. It has been reported that systemic administration or injection of moderate to high doses of corticosteroids into the joints or breast can cause a temporary decrease in lactation. A study of 46 women who delivered before 34 weeks of gestation found that administration of another corticosteroid (betamethasone, 11.4 mg intramuscularly twice 24 hours apart) 3 to 9 days before delivery delayed Phase II lactation and reduced average milk production within 10 days postpartum. Milk production was unaffected if the baby was delivered within 3 or 10 days of the mother receiving corticosteroid treatment. An equivalent dose of cortisone may have the same effect. A study of 87 pregnant women found that administration of betamethasone during pregnancy in the above manner led to a premature increase in lactose secretion. Although this increase was statistically significant, its clinical significance appears to be negligible. An equivalent dose of cortisone may 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 with the structure pregn-4-ene, substituted with hydroxyl groups at positions 17 and 21, and carbonyl groups at positions 3, 11, and 20. It is a metabolite in both humans and mice. It is a 17α-hydroxysteroid, 21-hydroxysteroid, 11-oxosteroid, 20-oxosteroid, C21 steroid, 3-oxo-Δ4 steroid, primary α-hydroxy ketone, tertiary α-hydroxy ketone, and glucocorticoid. It is derived from the hydride of pregnane. It is a naturally occurring glucocorticoid. It has been used as a replacement therapy for adrenal insufficiency and for anti-inflammatory treatment. Cortisone itself is inactive; it is converted in the liver to its active metabolite, hydrocortisone. (Excerpt from Martindale Pharmacopeia, 30th edition, p. 726) Cortisone is a corticosteroid. Its mechanism of action is as a corticosteroid hormone receptor agonist.
There are reports and data regarding the presence of cortisone in the human body.
Therapeutic cortisone is a corticosteroid with potent glucocorticoid activity. Therapeutic cortisone is an inactive precursor molecule of the active hormone cortisol, which is the product of cortisone hydroxylation by 11β-steroid dehydrogenase. Cortisol can raise blood pressure and blood sugar levels and suppress the immune system; therefore, cortisone is used to treat allergies or inflammation.
Cortisone is a steroid hormone synthesized and secreted by the adrenal glands and is essential for life. It participates in maintaining cardiovascular function, blood sugar balance, regulating inflammatory responses, and the metabolism of proteins, carbohydrates, and fats.
Cortisol is a naturally occurring glucocorticoid that has been used as a replacement therapy for adrenal insufficiency and for anti-inflammatory treatment. Cortisol itself is inactive; it is converted in the liver to the active metabolite, hydrocortisone. (Excerpt from Martindale Pharmacopeia, 30th edition, p. 726)
See also: Cortisone acetate (its active ingredient).

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

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.94 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.94 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.94 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)