• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.33 no.3
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• pp.115-124
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• 2020

Objectives : The purpose of this study is to investigate the effect and side effects of steroids on dermatitis and skin barrier through lipid metabolism. And to propose using Herbal medicine to suppress Steroid rebound and prevent side effects. Methods : We reviewed recent studies about the relationship between dermatitis, skin lipid, steroid, and herbal medicine through Google scholar. Results : In various inflammatory skin diseases, the corticosteroid is selected as the primary drug due to its strong anti-inflammatory and immunosuppressive effect. However, long-term use of steroids has a variety of side effects, especially lipid metabolism disruption, which aggravates skin barrier damage underlying various skin diseases and is more susceptible to inflammatory reactions. Conclusions : Herbal medicine is used as a comprehensive approach, and it can be used to reduce the frequency of steroid exposure by protecting against barrier damage by controlling anti-inflammatory, antioxidant, and systemic/sebaceous lipid metabolism and stratum corneum protein differentiation.

• IMMUNE NETWORK
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• v.3 no.2
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• pp.150-155
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• 2003

Background: We investigated the effect of donor marrow T cell depletion, administration of FK506, cyclosporin A (CSA), and 3-deazaadenosine (DZA) on graft versus host disease (GVHD) after allogeneic murine hematopoietic stem cell transplantation (HSCT). Methods: We used 4 to 6 week old Balb/c ($H-2^d$, recipient), and C3H/He ($H-2^k$, donor) mice. Total body irradiated recipients received $1{\times}10^7$ bone marrow cells (BM) and $0.5{\times}10^7$ splenocytes of donor under FK506 (36 mg/kg/day), CSA (5 mg/kg/day, 20 mg/kg/day), and DZA (45 mg/kg/day), which were injected intraperitoneally from day 1 to day 14 daily and then three times a week for another 2 weeks. To prevent the GVHD, irradiated Balb/c mice were transplanted with $1{\times}10^7$ rotor-off (R/O) cells of donor BM. The severity of GVHD was assessed daily by clinical scoring method. Results: All experimental groups were well grafted after HSCT. Mice in experimental group showed higher GVHD score and more rapid progression of GVHD than the mice with R/O cells (R/O group) (p<0.01). There were relatively low GVHD scores and slow progressions in FK506 and low dose CSAgroups than high dose CSA group (p<0.01). The survival was better in FK506 group than low dose CSA group. All mice treated with CSA died within 12 days after HSCT. The GVHD score in DZA group was low and slow in comparison with control group (p<0.05), but severity and progression were similar with low dose CSA group (p=0.11). All mice without immunosuppressive treatment died within 8 days, but all survived in R/O group (p<0.01). Survival in low dose CSA group was longer than in control group (p<0.05), but in high dose CSA group, survival was similar to control group. The survival benefit in DZA group was similar with low dose CSA group. FK506 group has the best survival benefit than other groups (p<0.01), comparable with R/O group (p=0.18), although probability of survival was 60%. Conclusion: We developed lethal GVHD model after allogeneic murine HSCT. In this model, immunosuppressive agents showed survival benefits in prevention of GVHD. DZA showed similar survival benefits to low dose CSA. We propose that DZA can be used as a new immunosuppressive agent to prevent GVHD after allogeneic HSCT.

• Tuberculosis and Respiratory Diseases
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• v.46 no.5
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• pp.685-696
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• 1999

Background : Idiopathic pulmonary fibrosis (IPF) is a diffuse inflammatory and fibrosing process that occurs within the interstitium and alveolus of the lung with invariably poor prognosis. The major problem in management of IPF results from the variable rate of disease progression and the difficulties in predicting the response to therapy. The purpose of this retrospective study was to evaluate the short-term efficacy of steroid and immunosuppressive therapy for IPF and to identify the pre-treatment determinants of favorable response. Method : Twenty patients of IPF were included. Diagnosis of IPF was proven by thoracoscopic lung biopsy and they were presumed to have active progressive disease. The baseline evaluation in these patients included clinical history, pulmonary function test, bronchoalveolar lavage (BAL), and chest high resolution computed tomography (HRCT). Fourteen patients received oral prednisolone treatment with initial dose of 1mg/kg/day for 8 to 12 weeks and then tapering to low-dose prednisolone (0.25mg/kg/day). Six patients who previously had experienced significant side effects to steroid received 2mg/kg/day of oral cyclophosphamide with or without low-dose prednisolone. Follow-up evaluation was performed after 6 months of therapy. If patients met more than one of followings, they were considered to be responders : (1) improvement of more than one grade in dyspnea index, (2) improvement in FVC or TLC more than 10% or improvement in DLco more than 20% (3) decreased extent of disease in chest HRCT findings. Result : One patient died of extrapulmonary cause after 3 month of therapy, and another patient gave up any further medical therapy due to side effect of steroid. Eventually medical records of 18 patients were analyzed. Nine of 18 patients were classified into responders and the other nine patients into nonresponders. The histopathologic diagnosis of the responders were all nonspecific interstitial pneumonia (NSIP) and that of nonresponders were all usual interstitial pneumonia (UIP) (p<0.001). The other significant differences between the two groups were female predominance (p<0.01), smoking history (p<0.001), severe grade of dyspnea (p<0.05), lymphocytosis in BAL fluid ($23.8{\pm}16.3%$ vs $7.8{\pm}3.6%$, p<0.05), and less honeycombing in chest HRCT findings (0% vs $9.2{\pm}2.3%$, p<0.001). Conclusion : Our results suggest that patients with histopathologic diagnosis of NSIP or lymphocytosis in BAL fluid are more likely to respond to steroid or immunosuppressive therapy. Clinical results in large numbers of IPF patients will be required to identify the independent variables.

• IMMUNE NETWORK
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• v.7 no.1
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• pp.10-17
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• 2007

Autoimmune arthritis, such as rheumatoid arthritis (RA), is a chronic inflammatory disorder that primarily affects the joints and then results in their progressive destruction. Effector Th cells have been classified as Th1 and Th2 subsets based on their cytokine expression profiles and immune regulatory function. Another subset of T cells termed Th17 was recendy discovered and known to selectively produce IL-17. Also, Th17 was shown to be generated by TGF${\beta}$ and IL-6 and maintained by IL-23. IL-17 is a proinflammatory cytokine that is considered to involve the development of various inflammatory autoimmune diseases such as RA, asthma, lupus, and allograft rejection. IL-17 is present in the sera, synovial fluids and synovial biopsies of most RA patient. IL-17 activates RA synovial fibroblasts to synthesize IL-6, IL-8 and VEGF via PI3K/Akt and NF-${\kappa}B$ dependent pathway. IL-17 increases IL-6 production, collagen destruction and collagen synthesis. In addition, it not only causes bone resorption but also increases osteoclastogenesis and fetal cartilage destruction. Inhibition of the IL-17 production may contribute a novel therapeutic approach along with potent anti-inflammatory effect and with less immunosuppressive effect on host defenses.

• Clinical and Experimental Reproductive Medicine
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• v.43 no.1
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• pp.15-25
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• 2016

Objective: In the present study, we aimed to evaluate the effects of high doses of dexamethasone (DEX) in early pregnancy on pregnancy outcomes. Methods: Pregnant BALB/c mice were treated with high-dose DEX in the experimental group or saline in the control group on gestational days (GDs) 0.5 to 4.5. Pregnant mice were sacrificed on GDs 7.5, 13.5, or 18.5 and their peripheral blood, placentas, fetuses, and uterine tissue were collected. Decidual and placenta cell supernatants were examined to evaluate the effect of DEX on the proliferation of mononuclear cells, the quantity of uterine macrophages and uterine natural killer (uNK) cells, and levels of progesterone and $17{\beta}-estradiol$, as determined by an 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We also were measured fetal and placental growth parameters on GD 18.5. Results: We found that high doses of DEX were associated with an increased abortion rate, enhancement of the immunosuppressive effect of the decidua, alterations in placental growth parameters, decreased progesterone and $17{\beta}-estradiol$ levels, and a reduced frequency of macrophages and uNK cells. Conclusion: Our data suggest that the high-dose administration of DEX during early pregnancy negatively affected pregnancy outcomes.

• Journal of Veterinary Clinics
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• v.16 no.2
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• pp.454-462
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• 1999

Corticosteroids have long been used for anti-inflammatory, anti-rheumatoid and other purposes in hospital. These effects may be due to inhibit immune reaction. So the animal given corticosteroids was more susceptible to infection because of immunosuppressive effect of corticosteroids. The purpose of this study was to investigate the effects of prednisolone on the lymphocyte subset in the spleen, immunoglobulin in serum, spleen weight, thymus weight and total WBC in peripheral blood. Mice were randomized into 3 groups. Each group has 24 mice. The small dosage group were given by 4 mg/kg/day of prednisolone for 4 days and the large dosage group were given by 8 mg/kg/day respectively. Prednisolone was suspended in saline and orally administered. Mice in control group were given saline alone. Eight mice in each group were sacrificed every week after administration of predisolone. The weight of thymus and spleen were mesured immediately. Lymphocytes were taken from spleen and these cells were analysed by flow cytometry. Also the concentration of total immunoglobulins in serum were assayed by enzyme-linked immunosorbant assay (ELISA). T cell, T-helper cell and T-cytotoxic cell were all significantly (P<0.05) decreased at 1 week after administration of predisolone and at 2 weeks they recovered similarly to that of control. Population of B cell showed various distribution. The concentration of total immunoglobulins in serum was not changed significantly. The weight ratio of spleen to body decreased significantly (P＜0.05) during predisolone administration but increased at 1 week later, Eventually the weight ratio was recovered to that of control at 2 weeks. The weight ratio of thymus to body decreased significantly (P<0.05) by prednisolone and recovered gradually up to normal ratio 2 weeks later.

• Biomolecules & Therapeutics
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• v.6 no.4
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• pp.389-394
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• 1998

Cyclosporine (CsA) is a major immunosuppressive drug used widely to prevent organ allograft rejection. fits potential organotoxicity by prolonged use is known to cause both direct tissue damage and indirect pharmacokinetic interactions with other drugs. This study was performed to determine the effect of nicardipine (NCP) on the pharmacokinetic parameters of CsA in Sprague-Dawley rats. Each rat was administered with CsA in saline-treated group or in NCP-treated group which was pretreated with NCP (5 mg/kg/12 hours, i.p.) for 6 days. The plasma CsA concentration were analyzed by reversed HPLC: UV system at 0.5, 1, 2, 4, 6, and 8 hours after bolus injection of CsA (10 mg/kg). Pharmacokinetic parameters (mean$\pm$ SD, n=7) such as initial plasma concentration (C(0)), mean residence time (MRT), steady-state volume of distribution (Vdss), terminal half-life (t$\frac{1}{2}$($\beta$)) and plasma clearance (CLp) of CsA in each groups (saline-group vs NCP-group) were determined as follows: C(0) (5.66$\pm$ 1.98 vs 17.98$\pm$2.36, p<0.01); Vdss (2.68$\pm$ 1.6 vs 0.94 $\pm$ 0.25, p<0.01); CLp (0.53 $\pm$0.18 vs 0.21 $\pm$0.06, p<0.01). Therefore, Our results indicate that nicardipine significantly affects the pharmacokinetic parameters of cyclosporme, especially C(0), Vdss, and CLp in NCP-treated group. We suggest that the significant pharmacokinetic interaction between cyclosporine and nicardipine should be considered and cyclosporine level should be closely monitored and dosage reduction made as necessary in clinical situation that was coadministered with CsA and NCP.

• Korean Journal of Pharmacognosy
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• v.17 no.3
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• pp.248-254
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• 1986

Effects of vinblastine(VLB) and vincristine(VCR) on cell-mediated immunity(CMI) were studied with the microcytotoxicity test(MCT) after normal or pre-sensitized Balb/c mice had been treated in vivo with a combination of two different doses of VLB or VCR(single dose of 20% and 60% $LD_{50}$, i.p.) at different times (from day -6 to day +4) plus allo-transplantation antigen(allo-TA, cells from C3H mice at day 0). The results were that $LD_{50}$ of VLB for female Balb/c mouse was 7.3mg/kg body weight (i.p.) and $LD_{50}$ of VCR was 4.3mg/kg body weight and that VLB and VCR acted as immunosuppressive agents on the primary CMI when administered after allo-TA(antigen-drug-phase), but showed no effect when administered prior to allo-TA(drug-antigen-phase). Change of doses of VLB and VCR(20% $LD_{50}$, 60% $LD_{50}$) caused quantitative or qualitative variations in the immunomodulating effects of these two drugs. Neither VLB nor VCR had any immunomodulating effect on the secondary CMI. Lastly, the results support that the four parameters (type of drug, sensitization status, time of drug treatment in relation to antigen injection, and drug dosis) are significant for the effects of the VLB and VCR on the CMI, and that VLB and VCR may inhibit the proliferation of antigen-stimulated T effector lymphocytes but not memory-cytotoxic T lymphocytes.

• Korean Journal of Veterinary Research
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• v.36 no.3
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• pp.647-655
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• 1996

To establish the effective ways to prevent bovine mastitis, the study has been performed to investigate the attributable factors causing down-regulation of immune responses in mammary gland of non-lactating cows. Lymphocytes from peripheral blood and mammary gland secretions(MGS) were obtained from normal healthy cows and mastitic cows, respectively. Lymphoblastogenesis were investigated carefully by adding different concentrations of supernatants collected from pure-cultures of neutrophils seperated from peripheral blood and MGS, respectively. The results obtained are as follows ; 1. Lymphoblastogenesis activity stimulated by Con A, PWM and PHA were significantly reduced in MGS from mastitic cows. 2. Supernatants collected from pure-culture of neutrophils separated both from peripheral blood and MGS showed inhibitory effect on mitogenic lymphoblastogenesis. 3. Supernatants from mammary gland neutrophils have shown 7 times more inhibitory activity than those from peripheral blood and this inhibitory effect was increased in proportion to increasing concentrations of supernatants when those were added to lymphoblast cells in culture.

• Parasites, Hosts and Diseases
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• v.35 no.3
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• pp.181-188
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• 1997

In order to clarify the effect of cryptosporidiosis on immune response, histopathological changes associated with experimentally occurring bursal cryptosporidiosis in chickens were chronologically observed as the first step. A total of 150 2-day-old chickens was each inoculated orally with a single dose of 5 × 105 Cryptospori,mum bailevi oocysts. The chickens showed a normal profile of oocyst shedding in droppings. The bursa indices throughout the experimental period indicated negligible reactions. Numerous cryptosporidia occurred in the microvillous border of bursal epithelium between days 4 and 16 postinoculation (PI). Appearance of the most mast cells was followed by a dramatic loss of the protozoa in the bursa of Fabricius (BF). The distribution of the coccidium coincided with heterophil infiltration in the epithelium and adjacent lamina propria. The histopathological lesion was marked diffuse chronic superficial purulent bursitis with heterophil infiltration in the epithelium and adjacent lamina proprla and mucosal epithelial hyperplasia. These results suggest that the bursitis may induce immunosuppressive effect.