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Somatic mutations that lead to hyperactivation of epidermal growth factor receptor (EGFR) signaling are detected in approximately 50% of lung adenocarcinoma in people from the Far East population and tyrosine kinase inhibitors are now the standard first line treatment for advanced disease. They have led to a doubling of progression-free survival and an increase in overall survival by more than 2 years. However, emergence of resistant clones has become the primary cause for treatment failure, and has created a new challenge in the daily management of patients with EGFR mutations. Identification of mechanisms leading to inhibitor resistance has led to new therapeutic modalities, some of which have now been adapted for patients with unsuccessful tyrosine kinase inhibitor treatment. In this review, we describe mechanisms of tyrosine kinase inhibitor resistance and the available strategies to overcoming resistance.

Background: Lung cancer is the most common cause of cancer related death. Alterations in gene sequence, structure, and expression have an important role in the pathogenesis of lung cancer. Fusion genes and alternative splicing of cancer-related genes have the potential to be oncogenic. In the current study, we performed RNA-sequencing (RNA-seq) to investigate potential fusion genes and alternative splicing in non-small cell lung cancer. Methods: RNA was isolated from lung tissues obtained from 86 subjects with lung cancer. The RNA samples from lung cancer and normal tissues were processed with RNA-seq using the HiSeq 2000 system. Fusion genes were evaluated using Defuse and ChimeraScan. Candidate fusion transcripts were validated by Sanger sequencing. Alternative splicing was analyzed using multivariate analysis of transcript sequencing and validated using quantitative real time polymerase chain reaction. Results: RNA-seq data identified oncogenic fusion genes EML4-ALK and SLC34A2-ROS1 in three of 86 normal-cancer paired samples. Nine distinct fusion transcripts were selected using DeFuse and ChimeraScan; of which, four fusion transcripts were validated by Sanger sequencing. In 33 squamous cell carcinoma, 29 tumor specific skipped exon events and six mutually exclusive exon events were identified. ITGB4 and PYCR1 were top genes that showed significant tumor specific splice variants. Conclusion: In conclusion, RNA-seq data identified novel potential fusion transcripts and splice variants. Further evaluation of their functional significance in the pathogenesis of lung cancer is required.

Background: Third-generation tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKIs) have proved efficacious in treating non-small cell lung cancer (NSCLC) patients with acquired resistance resulting from the T790M mutation. However, since almost 50% patients with the acquired resistance do not harbor the T790M mutation, retreatment with first- or second-generation EGFR-TKIs may be a more viable therapeutic option. Here, we identified positive response predictors to retreatment, in patients who switched to a different EGFR-TKI, following initial treatment failure. Methods: This study retrospectively reviewed the medical records of 42 NSCLC patients with EGFR mutations, whose cancers had progressed following initial treatment with gefitinib or erlotinib, and who had switched to a different firstgeneration EGFR-TKI during subsequent retreatment. To identify high response rate predictors in the changed EGFR-TKI retreatment, we analyzed the relationship between clinical and demographic parameters, and positive clinical outcomes, following retreatment with EGFR-TKI. Results: Overall, 30 (71.4%) patients received gefitinib and 12 (28.6%) patients received erlotinib as their first EGFR-TKI treatment. Following retreatment with a different EGFR-TKI, the overall response and disease control rates were 21.4% and 64.3%, respectively. There was no significant association between their overall responses. The median progressionfree survival (PFS) after retreatment was 2.0 months. However, PFS was significantly longer in patients whose time to progression was ≥10 months following initial EGFR-TKI treatment, who had a mutation of exon 19, or whose treatment interval was

Background Small cell lung cancer (SCLC) transformation during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in lung cancer has been suggested as one of possible resistance mechanisms. Methods We evaluated whether SCLC transformation or neuroendocrine (NE) differentiation can be found in the cell line model. In addition, we also investigated its effect on responses to conventional chemotherapeutic drugs of the SCLC treatment. Results Resistant cell lines to various kinds of EGFR-TKIs such as gefitinib, erlotinib, CL-387,785 and ZD6474 with A549, PC-9 and HCC827 lung adenocarcinoma cell lines were established. Among them, two resistant cell lines, A549/GR (resistant to gefitinib) and PC-9/ZDR (resistant to ZD6474) showed increased expressions of CD56 while increased synaptophysin, Rb, p16 and poly(ADP-ribose) polymerase were found only in A549/GR in western blotting, suggesting that NE differentiation occurred in A549/GR. A549/GR cells were more sensitive to etoposide and cisplatin, chemotherapeutic drugs for SCLC, compared to parental cells. Treatment with cAMP and IBMX induced synaptophysin and chromogranin A expression in A549 cells, which also made them more sensitive to etoposide and cisplatin than parental cells. Furthermore, we found a tissue sample from a patient which showed increased expressions of CD56 and synaptophysin after development of resistance to erlotinib. Conclusion NE differentiation can occur during acquisition of resistance to EGFR-TKI, leading to increased chemosensitivity.

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, are effective therapies for non-small cell lung cancer (NSCLC) patients whose tumors harbor somatic mutations in EGFR. The mutations are, however, only found in about 30% of Asian NSCLC patients and all patients ultimately develop resistance to these agents. Ionizing radiation has been shown to induce autophosphorylation of EGFR and activate its downstream signaling pathways. In the present study, we have tested whether the effect of gefitinib treatment can be enhanced after ionizing radiation. Methods: We compared the PC-9 and A549 cell line with its radiation-resistant derivatives after gefitinib treatment with cell proliferation and apoptosis assay. We also analyzed the effect of gefitinib after ionizing radiation in PC-9, A549, and NCI-H460 cells. Cell proliferation was determined by MTT assay and induction of apoptosis was evaluated by flow cytometry. Caspase 3 activation and PARP cleavage were evaluated by western blot analysis. Results: PC-9 cells having mutated EGFR and their radiation-resistant cells showed no significant difference in cell viability. However, radiation-resistant A549 cells were more sensitive to gefitinib than were their parental cells. This was attributable to an increased induction of apoptosis. Gefitinib-induced apoptosis increased significantly after radiation in cells with wild type EGFR including A549 and NCI-H460, but not in PC-9 cells with mutated EGFR. Caspase 3 activation and PARP cleavage accompanied these findings. Conclusion: The data suggest that gefitinib-induced apoptosis could increase after radiation in cells with wild type EGFR, but not in cells with mutated EGFR.

A hidden primary tumor presenting as an isolated Lung mass is a diagnostic challenge to physicians because the diagnosis of Lung cancer is Likely to be made if the histologic findings are not inconsistent with Lung cancer. A Large Lung mass was found incidentally in a 59-year-old man. Although adenocarcinoma was diagnosed by percutaneous needle biopsy, thyroid transcription factor-1(TTF-1) immunostaining was negative, raising suspicion that there was another primary site. There was no abnormal finding except for the Lung mass on a 18FDG-PET/CT scan and the patient did not complain of any discomfort. Finally, prostatic cancer was confirmed through the study of tumor markers and prostate-specific antigen(PSA) immunostaining. Because of the rare presentation of a single Lung mass in malignancies that have another primary site, physicians should carefully review all data before making a final diagnosis of Lung cancer.

Background: The pathophysiologic mechanisms of radiation-induced lung injury should be elucidated to enhance the therapeutic efficacy of radiotherapy and to manage patients exposed to serious radiation by accident. It has been suggested that pro-inflammatory cytokines play an important role in radiation-induced effect on the lung. This study was aimed to investigate changes in pro-inflammatory cytokines such as TNF- α, MIP-2, IL-1β and HMGB1, a newly recognized inflammatory mediator. Methods: The chests of BALB/c mice were selectively irradiated with single fraction of 20 Gy and then sacrificed at indicated times. Pathologic changes in the lung were examined after H&E staining. The expression level of pro-inflammatory cytokines was evaluated by ELISA kits in lung homogenate and in serum. Results: Radiation induced inflammatory changes and mild fibrosis in lung. Biphasic increase of TNF-α and IL-1β was found in lung homogenate at 4 hours and at 3 weeks after radiation. The elevation in the second phase tended to be more intense. However, there was no similar change in serum. MIP-2 level was slightly increased in lung homogenate at 4 hours, but not at 3 weeks. HMGB1 was increased at 3 weeks in serum while there was no significant change in lung homogenate. Conclusion: Radiation induced a biphasic increase in TNF-α and IL-1β. The effective control of second phase cytokine elevation should contribute to preventing severe lung fibrosis caused by radiation.

Lung cancer frequently metastasizes to distant organs. However, solitary metastasis to the pancreas, with lung cancer as the source, is very rare. Most metastatic cases of the pancreas tend to be discovered in patients with widely disseminated malignant disease. In addition, patients with pancreatic metastases are often asymptomatic, the metastatic lesions are found incidentally, and are misdiagnosed as primary pancreatic tumors. We described the case of a 63-year-old man who presented with abdominal pain and a pancreatic nodule. The patient underwent resection of primary lung cancer followed by pylorus preserving pancreatoduodenectomy. The pancreatic nodule was confirmed as a solitary metastasis from lung cancer.

Primary myelofibrosis is characterized by replacement of bone marrow with fibrotic tissue and the development of extramedullary hematopoiesis. Extramedullary hematopoiesis primarily involves the spleen and liver, but can also occur in the lungs. We report the case of an 80-year-old male who was admitted for evaluation of a lung mass and persistent thrombocytopenia. A percutaneous needle aspiration from the mass in the right lower lung showed myelopoietic cells with fatty tissue. A bone marrow biopsy revealed a hypercellular marrow with an increased number of atypical megakaryocytes. The final diagnosis was a prefibrotic stage of primary myelofibrosis leading to extramedullary hematopoiesis in the lung.

Henoch-Schonlein Purpura (HSP) is a systemic vasculitis involving small vessels with the deposition of immune complexes containing IgA and C3, which is characterized by associated skin, joint, renal, and gastrointestinal manifestations. Although there were several causes such as autoimmunity, infection, and drugs, it also can be presented as a form of vasculitidies associated with malignancies. We report a case of HSP developed during treatment for non-small cell lung cancer in a 66-year-old man. Multiple purpuric skin lesions occurred in both legs after the first cycle of chemotherapy, which was diagnosed as HSP by clinical and pathologic examinations. Due to the itching sensation, topical steroid was applied and the patient was improved 3 weeks later without a scheduled change in chemotherapy.

Background: Pain is one of the most troublesome problems caused by malignancy. We evaluated the change in pain status according to observance of NCCN guidelines in lung cancer patients. Methods: Lung cancer patients complaining of pain at admission were examined. The pain was assessed with visual analogue scale (VAS) for 20 days and moderate-to-severe pain was defined as more than VAS level 3. The guideline observance was classified as high (more than 80%), medium (50∼79%) and low (less than 50%). Results: Among the total 91 lung cancer patients with pain, 34 patients (37%) had moderate-to-severe pain. Their average VAS score at admission was 5.6. It decreased to 2.9 after a 20-day period of pain management. The time to reach a VAS less than 3 was 3 days in a high guideline observance group, while it took 6 days in a low observance group. In addition, the pain in the high observance group was controlled to less than 3 VAS level in 86% of patients, whereas only 25% of patients in the low observance group succeeded. Conclusion: Pain was more effectively controlled when the dose of drugs was modified according to NCCN guidelines in lung cancer patients indicating the importance of guideline observance in pain management.

Summary Prompt and proper discovery of cause is important in lung cancer patients with signs and symptoms of in-testinal obstruction because approach for treatment may differ according to its etiology and emergency operation can often be required to prevent more severe complic-ations. In this report, we present two different causes of intestinal obstruction in lung cancer. Physicians need to be aware of these possibilities to differentiate the cause of intestinal obstruction in patients with lung cancer. References 1. Kim MS, Kook EH, Ahn SH, Jeon SY, Yoon JH, Han MS, et al. Gastrointestinal metastasis of lung cancer with special emphasis on a long-term survivor after op-eration. J Cancer Res Clin Oncol 2009;135:297-301. 2. Yang CJ, Hwang JJ, Kang WY, Chong IW, Wang TH, Sheu CC, et al. Gastro-intestinal metastasis of primary lung carcinoma: clinical presentations and outcome. Lung Cancer 2006;54:319-23. 3. Antler AS, Ough Y, Pitchumoni CS, Davidian M, Thelmo W. Gastrointestinal metastases from malignant tumors of the lung. Cancer 1982;49:170-2. 4. McNeill PM, Wagman LD, Neifeld JP. Small bowel meta-stases from primary carcinoma of the lung. Cancer 1987;59:1486-9. 5. Yoshimoto A, Kasahara K, Kawashima A. Gastrointesti-nal metastases from primary lung cancer. Eur J Cancer 2006;42:3157-60. 6. Ise N, Kotanagi H, Morii M, Yasui O, Ito M, Koyama K, et al. Small bowel perforation caused by metastasis from an extra-abdominal malignancy: report of three cases. Surg Today 2001;31:358-62. 7. Milner EA, Cioffi WG, McManus WF, Pruitt BA Jr. Sup-erior mesenteric artery syndrome in a burn patient. Nutr Clin Pract 1993;8:264-6. 8. Pentlow BD, Dent RG. Acute vascular compression of the duodenum in anorexia nervosa. Br J Surg 1981;68: 665-6. 9. Coster DD, Stubbs DH, Sidney DT. Duodenal obstru-ction by abdominal aortic aneurysms. Am J Gastroen-terol 1988;83:981-4.10. Derincek A, Wood KB, Muench CA. Superior mesen-teric artery syndrome following correction of kyphosis

An intramedullary spinal cord metastasis (ISCM) rarely develops in systemic cancer but is indicative of a poor prognosis. A 56-year-old man was admitted due to weakness of the lower extremities. He had received radiotherapy 3 months prior for a brain metastasis that had developed 1 year after achieving a complete response from chemotherapy for extended stage small cell lung cancer. Although the brain lesion had improved partially, ISCM from the cervical to lumbar-sacral spinal cords, which was accompanied by a leptomeningeal dissemination, was diagnosed based on magnetic resonance imaging of the spine and cerebrospinal fluid cytology. Finally, he died of sudden cardiac arrest during treatment. This is the first case of ISCM involving the whole spinal segments. Physicians should be aware of the subsequent development of ISCM in lung cancer patients with a previously known brain metastasis who present with new neurological symptoms.

Although a paradoxical response of tuberculosis to antituberculous therapy is not a rare phenomenon, it can be a clinical challenge to differentiate a paradoxical response from treatment failure. A 25-year-old woman was admitted for miliary lung nodules and multiple intracranial nodules. Antituberculous treatment was started with a preliminary diagnosis of tuberculosis based on the history and clinical findings. After one month, the military lung nodules improved while the intracranial nodules increased in size and number. Based on a stereotactic biopsy, it was confirmed that the intracranial lesions were tuberculomas. Although the therapeutic regimen was not changed, the symptoms eventually were ameliorated and the intracranial nodules improved two months later.

Tumor lysis syndrome is a life-threatening complication of anti-cancer therapy that typically occurs in patients with large, rapidly growing and treatment-sensitive tumors such as high-grade lymphomas and acute leukemias. However, its incidence in solid tumors has been known to be very low. Tumor lysis syndrome in solid tumors has a high mortality rate owing to the lack of prophylactic therapy to prevent this complication. We report a case of fatal tumor lysis syndrome developed during chemotherapy in extensive-stage small cell lung cancer, along with a brief review of the relevant literature considering the rarity of this manifestation in solid tumor. (Tuberc Respir Dis 2008;64:215-218)

Gefitinib is a novel drug used to treat advanced non-small cell lung cancer. However, drug-related interstitial pneumonia is a major life-threatening side effect, which has a worldwide prevalence of 0.3-0.4%. In Japan, the prevalence is high as 3-4% but the actual frequency in Korea has not been officially assessed. We report two cases of gefitinib-induced interstitial lung disease during the treatment of non-small cell lung cancer. High-resolution computerized tomography (HRCT) of one case showed nonspecific ground glass opacity and the chest x-ray of another case showed diffuse bilateral ground glass opacity. The former patient showed a rapid good response to corticosteroid treatment whereas the latter died despite receiving aggressive treatment with high dose corticosteroid and empirical antibiotics.

Pulmonary alveolar proteinosis is a rare disorder that is characterized by the abundant accumulation of surfactant-derived material within the alveolar spaces and distal bronchioles. Although the findings of homogenous ground-glass opacities overlaid by thickened septa, which form a "crazy paving" pattern on high-resolution computed tomography, can assist in making a diagnosis, a lung biopsy is usually required. This disorder has a variable clinical course, from spontaneous resolution to respiratory failure and death. While a whole lung lavage has been the standard treatment since the early 1960s, GM-CSF therapy has been attempted based on the recently suggested pathogenetic mechanism. We report a case of pulmonary alveolar proteinosis that resolved spontaneously after an open lung biopsy.

A radiation recall reaction refers to an inflammatory reaction at previous irradiated areas subsequent to the administration of a variety of pharmacological agents. The skin is the major site of radiation recall reactons with the muscle and internal organs being less commonly affected. These reactions usually occur days to weeks after exposure to the causative agents. We report a case of gemcitabine-induced radiation recall dermato-myositis the developed in a female patient with a metastatic non-small cell lung cancer. She had received a palliative radiation therapy of 3900 cGy to the metastatic lesion on the femur shaft prior to chemotherapy. The pain, swelling and erythema of the left thigh resolved after the cessation of gemcitabine and the use of a systemic steroid.

Address for correspondence : Cheol Hyeon Kim, M.D. Department of Internal Medicine, Korea Cancer Center Hospital, 215-4, Gongneung-Dong, Nowon-Ku, Seoul 139-706, Korea Phone : 02-970-1209 Fax : 02-970-2401 E-mail : cheol@kcch.re.kr Received : Jun. 15. 2004. Accepted : Jul. 15. 2004. Actinomycosis is an indolent infectious disease characterized by pyogenic response and necrosis, followed by intense fibrosis. The main forms of human actinomycosis are cervicofacial, pulmonary, and abdominopelvic type. Pulmonary actinomycosis accounts for 15% to 20% of total cases and unfortunately, clinical manifestations and radiologic findings are nonspecific. Small pleural effusion or empyema may develop in advanced disease but massive empyema is infrequent and rarely reported. We report a case of huge empyema caused by pulmonary actinomycosis in a 55 year-old man, presented with one-month history of productive cough and fever. The CT scan revealed a huge cavity with air-fluid level occupying the left hemithorax. Empyema caused by actinomycosis was confirmed microscopically by demonstration of sulfur granules in empyema sac through thracotomy. Decortication and surgical resection of empyema sac and destructed lung was accomplished and followed by intravenous infusion of penicillin G. (Tuberc Respir Dis 2004; 57:579-583)

Catamenial hemoptysis is syndrome characterized by bleeding from the bronchial trees and lungs that occurs synchronously with the female menstrual cycle. Etiologic mechanism of pulmonary endometriosis is still controversial, and the diagnosis is usually made on the basis of the clinical history and exclusion of other causes of recurrent hemoptysis. Serial computed tomograms of the chest during and in the interval between menstruations have been proved to be a useful confirmatory test. We experienced a 33-year-old female patient who had been previously diagnosed as pelvic endometriosis pathologically, experienced cyclic hemoptysis during menstruations. The diagnosis of pulmonary endometriosis was made based on her history and changes in the character of the lesions as documented on radiologic studies of the chest. She was treated successfully with GnRH analogue and there is no evidence of recurrence.

An idiopathic mediastinal fibrosis is a rare disease with an unknown etiology. It is a benign condition in which a fibrosis of the soft tissue and chronic inflammation occurs within the mediastinum. This leads to a constriction and obliteration of the adjacent mediastinal structures, particularly the great veins. This can result in a variety of clinical conditions depending on the anatomic location of the disease. Here, we report a case of an idiopathic mediastinal fibrosis with vocal cord palsy, which was confirmed by a biopsy with a thoracotomy. Postoperative medical treatment using prednisolone and tranilast was performed.

Lymphocytic interstitial pneumonia(LIP) is characterized by a massive infiltration of the interstitium of the lung by mature lymphocytes, plasma cells and reticuloendothelial cells. LIP may be associated with autoimmune diseases including Sjgrens syndrome, SLE, myasthenia gravis, pernicious anemia, autoimmune hemolytic anemia, and HIV or an EB virus infection. There is a possibility of LIP progressing to a pulmonary or systemic lymphoma. The therapeutic response to corticosteroids and/or immunosuppressive drugs varies. Here we report a case of LIP that was diagnosed by an open lung biopsy and clonality study. The patient was a 36 year-old man without autoimmune disease or HIV infection. He was admitted as a result of severe hypoxemia showing of 48.3mmHg. The patient was treated with corticosteroids after the diagnosis and had fully recovered without a sequalae or relapse.

Background: IFN- plays an important role in host response to intracellular organisms such as mycobacterium. Human infection with mycobacterium leads to a wide variety of outcomes, ranging from asymptomatic infection to widespread and rapidly fatal disease. Recent reports suggest that alteration of the function of IFN- caused by a defective IFN- receptor gene can explain different host response to mycobacterium. In this study, we investigated the role of IFN- in the development of chronic refractory tuberculosis. Methods: The LPS-induced TNF- production with or without IFN- priming was compared by using monocytes taken from recently diagnosed tuberculosis, chronic refractory tuberculosis patients and controls. And the IFN- receptor was measured by indirect fluorescent antibody technique to know whether change in the priming effect of IFN- is related to IFN- receptor deficiency or not. Results: The ratio of TNF- produced in response to stimulation with INF- and LPS to LPS alone was in controls, in recently diagnosed tuberculosis patients and in chronic refractory tuberculosis patients. The priming effect of IFN- significantly decreased in chronic refractory tuberculosis patients compared with that in controls(p=0.002). However, IFN- receptor deficiency was detected in one of chronic refractory tuberculosis patients. Conclusion: The decrease of the priming effect of IFN- may play an important role in the development of chronic refractory tuberculosis, and in some patients, this may be related to the IFN- receptor deficiency.

Objectives: Although outbreak of MDR Tb has been a recent problem in western countries, it has been a longstanding problem in Korea. The poor outcome of MDR Tb is mainly due to poor compliance, high rate of side reaction of secondary drugs, and limitation in number of available drugs. Thus, to improve the outcome of MDR Tb, it is crucial to make individualized adequate prescription based on the knowledge of the patterns of resistance to each drugs in the community as well as the natural history. The purpose of present study is to evaluate the clinical features of Korean MDR Tb patients including patterns of drug resistance and success rate of treatment which was prescribed according to the sensitivity tests. Methods: Retroscpective analysis of 71 Korean patients with MDR Tb was made. All strains isolated from patients showed resistence to at least two first line drugs. Patients profile, previous treatment history, patterns of drug resistance, outcome of treatment was analysed. Initial treatment regimen was selected according to the previous treatment history and was modified according to the sensitivity reports. The regimen was composed to include at least 4 sensitive drugs when possible. Results: The patients showed resistance to 4.1 drugs on average. 90% of them were resistant to INH and RFP. Among 71 patients, 35 patients(49%) had cavitary lesions in CXR. Treatment outcome was analysed in 55 patients. 35 patients(67%) were improved after treatment and 18 patients(33%) showed treatment failure. 5 patients showed primary resistance. Treatment outcome could be evaluated in 4 of them and all showed improvement after treatment. 14 patients(20%) had to change their regimens due to drug side effects. The most frequent side effect was elevation of liver enzymes(6 patients). Others included dizziness, hyperuricemia, tinnitus, skin rash, GI troubles. More than 50% of side effects developed within 3 months. In repeated drug sensitivity test, the concordance rate of resistance to INH was 100% and RFP 98%. EMB, PZA showed 80% concordance rate. But in the other drugs, the concordances were less than 50%. Operation was done in 5 patient - 1 patients as a adjunctive means of chemotherapy -. In that case, negative conversion of sputum AFB was done. Conclusion: 2/3 patients of multidrug-resistant tuberculosis were improved by appropriate prescription and regular medication suggesting that more aggressive management and monitoring is indicated in multidrug-resistant tuberculosis.

We report the first case of summer-type hypersensitivity pneumonitis(SHP) in Korea diagnosed by positive serum antibodies to Trichosporon cutaneum. Hypersensitivity pneumonitis(HP) has been commonly classified as an occupational respiratory diseases. However, evidence that sensitizing organisms can also contaminate and cause pulmonary diseases in home environment has been increasing. One such disease is SHP. In Japan, 75% of cases with HP are SHP. Even though there has been no known SHP case in Korea yet, there has been high possibility of SHPs in Korea because our country has areas which have hot and humid summer climate similar to Japan. This first case of SHP in Korea suggests that there may be another cases in Korea and nation-wide survey may be required. We report here the first confirmed case of SHP in Korea.

Background: Peripheral blood monocytes are important immune effector cells that play a fundamental role in cellular immunity. In addition to their antigen-presenting and phagocytic activities, monocytes/macrophage produce a vast array of regulatory and chemotactic cytokines. Interleukin-8(IL-8), a potent neutrophil-activating and chemotactic peptide, is produced in large quantities by mononuclear phagocytes and may be an important mediator of local and systemic inflammation. Overexpression by IL-8 of such inflammation may be an important step of tissue injury frequently seen in inflammatory reaction. So it could be hypothesized that the agents which block the production of IL-8 can decrease the inflammatory reaction and tissue injury. To evaluate this, we described the effect of Dexamethasone, , Indomethacin and Interferon-(IFN-) on IL-8 mRNA and protein expression from LPS-stimulated human peripheral blood monocytes(PBMC). Method: PBMC was isolated from healthy volunteers. To evaluate the effect of Dexamethasone, & Indomethacin, these drug were treated for 1 hour before and after LPS stimulation and IFN- was only treated I hour before the LPS stimulation. Northern blot analysis for IL-8 mRNA and ELISA for immunoreactive IL-8 protein in culture supernatant were performed. We repeated above experiment three times for Northern blot analysis and two times for ELISA and got the same result. Results: 1) Pre- and post-treatment of Dexamethasone suppressed both the LPS stimulated IL-8 mRNA expression and IL-8 protein release in PBMC. 2) IFN- pre-treatment suppressed the IL-8 mRNA expression and IL-8 protein release in unstimulated cells. 3) In LPS stimulated cells, IFN- suppressed the IL-8 mRNA expression but IL-8 protein release suppression was not observed. 4) and Indomethacin exert no effect on the LPS-stimulated IL-8 mRNA and protein expression in concentration used in this experiment (, Indomethacin; ). Conclusion: One of the mechanism of antiinflammatory action of Dexamethasone can be explained by the suppressing effect of IL-8 production in some extent and by this antiinflammatory effect, dexamethasone can be used to suppress local and systemic inflammation mediated by IL-8.