• Asian-Australasian Journal of Animal Sciences
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• v.25 no.7
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• pp.1021-1028
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• 2012

Peripheral blood mononuclear cells (PBMCs) discriminate microbial pathogens and induce T-cell responses of appropriate effector phenotype accordingly. Toll-like receptors (TLRs), in part, mediate this microbial recognition and differentiation while the development of T-cell effector functions critically depends on the release of Th1- or Th2- type cytokines. In the present study, buffalo PBMCs were stimulated under in vitro culture conditions by Bacillus subtilis cell wall petidoglycan, a TLR2 ligand, in a dose- and time- dependent manner. The expression of TLR2 as well as the subsequent differential induction of the Th1 and Th2 type cytokines was measured. Stimulation was analyzed across five doses of peptidoglycan ($10{\mu}g/ml$, $20{\mu}g/ml$, $30{\mu}g/ml$, $40{\mu}g/ml$ and $50{\mu}g/ml$) for 3 h, 12 h, 24 h and 36 h incubation periods. We observed the induction of TLR2 expression in a dose- and time-dependent manner and the peptidoglycan induced tolerance beyond $30{\mu}g/ml$ dose at all incubation periods. The correlation between peptidoglycan stimulation and TLR2 induction was found positive at all doses and for all incubation periods. Increased production of all the cytokines was observed at low doses for 3 h incubation, but the expression of IL-4 was relatively higher than IL-12 at the higher antigen doses, indicating tailoring towards Th2 response. At 12 h incubation, there was a pronounced decrease in IL-4 and IL-10 expression relative to IL-12 in a dose- dependent manner, indicating skewing to Th1 polarization. The expression of IL-12 was highest for all doses across all the incubation intervals at 24 h incubation, indicating Th1 polarization. The relative expression of TNF-${\alpha}$ and IFN-${\gamma}$ was also higher while that of IL-4 and IL-10 showed a decrease. For 36 h incubation, at low doses, relative increase in the expression of IL-4 and IL-10 was observed which decreased at higher doses, as did the expression of all other cytokines. The exhaustion of cytokine production at 36 h indicated that PBMCs became refractory to further stimulation. It can be concluded from this study that the cytokine response to sPGN initially was of Th2 type which skews, more pronouncedly, to Th1 type with time till the cells become refractory to further stimulation.

• Development and Reproduction
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• v.21 no.4
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• pp.361-370
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• 2017

Koi herpesvirus (KHV), also known as Cyprinid herpes virus 3 (Cyprinid 3) is lethal disease in common carp and koi (Cyprinus carpio). Two different groups (KK and RK) were infected KHV by intraperitoneal injection. Fish for gene expression analysis were sampled at 0 h, 12 h, 24 h, 48 h and 72 h post infection (p.i). The results showed that two immune related gene, Interferons (INFs) ${\alpha}{\beta}$ and Interleukin (IL)-12 p35 induced a high response in RK. The IL-12 p35 cytokine and Toll-like receptor (TLR) 9 were significantly high expressed on 48 h post infection (p.i) in RK as compared to the KK. The histopatological examination reveals focal necrosis in liver and infiltrate of lymphocytes in spleen of KK as compared to the RK. In immunohistochemistry analysis, the KHV protein high expressed in the infected kidney cell and slenocyte of KK. Therefore, the expression of IL-12 p35, IFN ${\alpha}{\beta}$ and TLR 9 may provide a potentially genes related with KHV resistance in Koi and red common carp ${\times}$ koi.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.306.1-306.1
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• 2002

Cefodizime has originally been developed for treating infections as antibiotics. However. according to some of recent studies. cefodizime. a third generation cephalosporin. may potentially have the capability of stimulating chemotactic activity of neutrophils and monocytes as well as the strong immuno-modulator. In this study. we studied to learn about the expressive effect of dentritic cells and macrophage. With this background. We have studied to see if cefodizime can be a potential substance inducing an immunological function in dendritic cells and peritoneal macrophages. IL-12 activates NK cell and macrophage, and shows antiviral effect by excreting INF-${\gamma}$. In vitro. total RNAs were extracted from murine dentritic cell at 4, 8, 12, 24hr after the application of 10, 50, 100${\gamma}g$/ml of cefodizime wighout other stimulators. And we analyzed IL-12 mRNA using RT-PCR method. In conclusion. IL-12 mRNA was increased. and the results suggest that cefodizime activate TH1 cell induction, CTL differentiation as well as accelerating the increase of NK. LAK cell.

• Journal of Veterinary Clinics
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• v.20 no.4
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• pp.478-481
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• 2003

Canine juvenile cellulitis (CJC) is a well-recognized lymphocutaneous disease that is seen in young dogs. CJC seemed to be immunologic disorder and may have a hereditary aspect. Exact pathogenesis and cytokine regulation on the immune system of CJC are not clear. CJC was diagnosed in two puppies hospitalized in Veterinary Teaching Hospital of Chungbuk National University. To investigate the cytokine regulation on CJC, RT-PCR was performed with CJC affected dogs. RT-PCR 1 was performed with whole blood sample (CJC-B) and fine needle aspirates of the inguinal lymph node (CJC-LN) from case 1-dog, which included $TNF-\alpha,$ $IL-1\beta,$ $IFN-\gamma,$ IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 and $\beta-actin.$ Blood sample from a normal dog (N-B) served for a negative control of RT-PCR 1 (case 1). $IFN-\gamma,$ IL-2, IL-4, IL-5, IL-8, IL-10 and IL-12 transcripts were not expressed in all sample. $TNF-\alpha$ and $IL-1\beta,$ were not transcripted from CJC-B but from CJC-LN. On RT-PCR 2 (case 2), submandibular lymph node aspirates were used and $TNF-\alpha,$ IL-10, $IFN-\gamma$ and $IL-1\beta$ were expressed. $TNF-\alpha,$ 1L-10 and $IFN-\gamma$ were secreted from activated macrophages enhance the inflammation in tissue. These results imply that abnormally increased macrophages secret $TNF-\alpha$ and $IL-1\beta$ in the affected lymph nodes, which attract neutrophils and cause inflammation in CJC.

• Herbal Formula Science
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• v.16 no.1
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• pp.185-205
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• 2008

The purpose of this study is to determine whether the clinical activity of patients with atopic dermatitis(AD) correlate with their serum cytokine levels. 86 patients with AD were treated with KHS, YMH and GHT. On each visit to the clinic, their skin status was evaluated using the SCORAD index and serum IL-4, $IFN-{\gamma}$, IL-12, IL-13, IL-2 and IL-10 were measured by ELISA. After oral administration of herbal medicine, patients' skin status and subjective parameters such as pruritus and sleeplessness were significantly improved according to regression analysis. In particular, patients aged 0-9 showed stronger responses to treatment, which implies that the younger patients aged, the easier the treatment by herbal formula became. In analysis of the type of chosen herbal medicines, YMH treated group showed a stronger response in reduction of affected lesion, intensity of a lesion and subjective symptoms, while KHS treated group showed the least reduction. The levels of serum IL-4, $IFN-{\gamma}$ and IL-2 correlated with disease activity. Moreover, in patients under 0-9, the IL-4 level had a corrleation with disease activity; patients under 10-19 showed a correlation between the levels of IL-4 and IL-2 and disease activity; patients under 20-29 showed a correlation between the levels of IL-2, IL-12 and $IFN-{\gamma}$ and disease activity. In comparison with chosen herbal medicines, the groups treated with YMH or GHT treated group showed a correlation between the levels of IL-4, IL-12 and IL-2 and disease activity while KHS treated group did not. Our data suggest that serum levels of IL-4 and IL-13 are good indicators of clinical improvement in treating AD.

• Journal of Veterinary Clinics
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• v.38 no.1
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• pp.27-31
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• 2021

Shea butter (Vitellaria paradoxa) is a fat extracted from shea tree nuts and contains relatively high levels of non-glycerides. Triterpenes, the main non-glyceride component, exhibit a variety of biological activities such as antitumor, antibacterial, and anti-inflammatory. Shea butter extract (SBE) has been used to treat various skin problems such as burns, eczema, and rash in human medicine, but little is known about the activity of SBE on canine skin. This study evaluated the cytotoxicity and anti-inflammatory effect of SBE in canine keratinocytes. Cytotoxicity of lipopolysaccharide (LPS, 5-50 ng/mL) and SBE (50-200 ㎍/mL) was evaluated using the CCK-8 assay. Non-cytotoxic concentrations of LPS and SBE were administered to canine cell cultures to evaluate anti-inflammatory effects. To evaluate the anti-inflammatory activity of SBE, the levels of IL-1β, IL-8, IL-12, and TNF-α were measured using ELISA kits. The concentration of each cytokine was quantified in control, LPS-treated, LPS + SBE-treated groups. Increased levels of IL-1β, IL-8, and IL-12 were found in LPS-treated groups relative to control groups. LPS + SBE-treated groups showed a lower level of IL-1β, IL-8, and IL-12 than LPS-treated groups. These results suggest that SBE may have application as a topical agent for canine inflammatory skin diseases. However, further in vivo study is needed to evaluate the safety and efficacy of SBE in dogs.

• Tuberculosis and Respiratory Diseases
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• v.50 no.4
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• pp.473-483
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• 2001

Background : There are only a few studies regarding the causes of treatment failure for tuberculosis. Therefore, this study aimed to determine the causes of intractable tuberculosis. Methods : M. tuberculosis, differentiated MOTT (Mycobacterium Other Than Tuberculosis) were isolated, and the RFLP (Restriction fragments length polymorphisms) pattern was analyzed from 204 patients with pulmonary tuberculosis and 53 suffering from neck tuberculosis. The IL-$1{\beta}$, IL-12, $^*1\;IFN{\gamma}$ and $^*2\;TNF{\alpha}$ blood levels were measured. All patients were regularly followed for 18 months after treatment. Results : There was no correlation between the RFLP patterns of M. tuberculosis treatment failure. From the 204 cases, 31.9% were intractable. The characteristics of patients with intractable tuberculosis were old age, being male and recurrent cases. The causes of treatment failure were identified as follows ; a decrease in the IL-12(59.4%) concentration, drug resistant strain(54.7%), irregular medication(15.4%), MOTT(6.2%) and a heavy infection(4.6%). The causes of all cases of intractable tuberculosis could be investigated. The IL-12 concentration in the blood was significantly lower in the intractable cases, where it disclosed a maximum sensitivity(64.7%) and specificity(75.4%) at 165.0 pg/mL. Most of the 53 cases of neck node tuberculosis were treated successfully. Therefore, we were unable to analyze the cause of treatment failure. Conclusion : A decrease in the blood IL-12 concentration and drug resistant strains were identified as the most significant causes of treatment failure for tuberculosis. In Korea, infection by clusters were prevalent, but no difference in the clinical course between clusters and non-clusters could be found.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5733-5739
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• 2014

Background: Breast cancer is the most common female malignancy in the world. Beta glucan can be a hematopoietic and an immune modulator agent in cancer patients. The aim of this trial was to determine the effect of beta glucan on white blood cell counts and serum levels of IL-4 and IL-12 in women with breast cancer undergoing chemotherapy. Materials and Methods: This randomized double-blind placebo-controlled clinical trial was conducted on 30 women with breast carcinoma aged 28-65 years. The eligible participants were randomly assigned to intervention (n=15) or placebo (n=15) groups using a block randomization procedure with matching based on age, course of chemotherapy and menopause status. Patients in the intervention group received two 10-mg capsules of soluble 1-3, 1-6, D-beta glucan daily and the control group receiving placebo during 21 days, the interval between two courses of chemotherapy. White blood cells, neuthrophil, lymphocyte and monocyte counts as well as serum levels of IL-4 and IL-12 were measured at baseline and at the end of the study as primary outcomes of the study. Results: In both groups white blood cell counts decreased after 21 days of the intervention, however in the beta glucan group, WBC was less decreased non significantly than the placebo group. At the end of the study, the change in the serum level of IL-4 in the beta glucan group in comparison with the placebo group was statistically significant (p=0.001). The serum level of IL-12 in the beta glucan group statistically increased (p=0.03) and comparison between two groups at the end of the study was significant after adjusting for baseline values and covariates (p=0.007). Conclusions: The findings suggest that beta glucan can be useful as a complementary or adjuvant therapy and immunomodulary agent in breast cancer patients in combination with cancer therapies, but further studies are needed for confirmation.

• Journal of Oriental Neuropsychiatry
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• v.16 no.1
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• pp.81-96
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• 2005

This experiment was designed to investigate the effect of Dichroa febrifuga(DIF) on the Alzheimer’s disease. The effects of DIF extract on $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA of THP-1 cell treated by $A{\beta}$ plus LPS and amyloid precursor proteins(APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ and AChE activity of PC-12 cell lysate treated by $A{\beta}$ plus $rIL-1{\beta}$ and behavior of memory deficit mice induced by scopolamine and mice glucose, uric acid, AChE activity of memory deficit rats induced by scopolamine were investigated, respectively. The results were summarized as follows ; 1. DIF extract suppressed APP, AChE, GFAP mRNA in PC-12 cell treated by $A{\beta}$. 2. DIF extract suppressed $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA in THP-1 cell treated by LPS. 3. DIF extract suppressed AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$. 4. DIF extract increased glucose, decreased uric acid and AChE significantly in the serum of the memory deficit rats induced by scopolamine. 5. DIF extract group showed significantly inhibitory effect on the memory deficit of mice induced by scopolamine in the experiment of Morris water maze. According to the above results, it is suggested that DIF extract might be usefully applied for prevention and treatment of Alzheimer’s disease and memory deficit.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.835-845
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• 1998

Background: Silica-induced lung diseases is characterized by the accumulation of inflammatory cells at early stage and fibrosis in pulmonary parenchyma and interstitium at late stage. As a consequence of inflammation, silicosis is accompanied with the expansion of interstitial collagen and the formation of fibrotic nodule. In this process, several kinds of lung cells produce cytokines which can amplify and modulate pulmonary fibrosis. The alveolar macrophage is a potent source of proflammatory cytokines and growth factor. But in the process of silicotic inflammation and fibrosis, there are many changes of the kinetics in cytokine network. And the sources of cytokines in each phase are not well known. Method: 2.5 mg of silica was instillated into the lung of C57BL/6J mice. After intratracheal instillation of silica, the lungs were removed for imunohistochemical stain at 1, 2, 7 day, 2, 4, 8, 12 week, respectively. We investigated the expression of IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ in lung tissue. Results: 1) The expression of IL-6 increased from 1 day after exposure to 8 weeks in vascular endothelium. Also peribronchial area were stained for IL-6 from 7 days and reached the peak level for 4 weeks. 2) The IL-1 $\beta$ was expressed weakly at the alveolar and peribronchial area through 12 weeks. 3) The TNF-$\alpha$ expressed strongly at alveolar and bronchial epithelia during early stage and maintained for 12 weeks. 4) TGF-$\beta$ was expressed strongly at bronchial epithelia and peribronchial area after 1 week and the strongest at 8 weeks. Conclusion: The results above suggests IL-6, TNF-$\alpha$ appear to be a early inflammatory response in silica induced lung fibrosis and TGF-$\beta$ play a major role in the maintenance and modulation of fibrosis in lung tissue. And the regulation of TNF-$\alpha$ production will be a key role in modultion of silica-induced fibrosis.