Effect of Hypoxia on Cytokine Production in Rheumatoid Fibroblast-Like Synoviocytes / 대한류마티스학회지

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by increased production of cytokines, proliferation of fibroblast-like synoviocytes (FLS) and joint destruction. It is well known that the involved joints in RA are hypoxic. Hypoxia may play a role in the pathogenesis of RA. We thought that hypoxia might alter the production of cytokines by FLS and these changes could affect the biologic behaviors of FLS. Based on that, we investigated whether hypoxia affects the production of cytokines in FLS and the effect of these changes on matrix metalloproteinases (MMPs) expression. METHODS: Fibroblast-like synoviocytes from human rheumatoid synovial tissue obtained duringjoint replacement surgery were cultured in vitro. Hypoxic culture was performed by incubating cells in BBL? Gaspak pouchTM anaerobic system. After incubation under hypoxic condition for 24 hr, the concentrations of various cytokines in culture supernatants were determined by ELISA. To determine the effect of highly expressed cytokines on MMP expression, we performed ELISA of MMP-1, MMP-2 and MMP-3 in cultured FLS, after stimulation with respective cytokines. RESULTS: In hypoxic state, IL-6, IL-8 and vascular endothelial growth factor (VEGF) concentrations were significantly increased compared to those in normoxic condition. However, there were little differences in IL-1, IL-2, IL-4, TNF-alpha and TGF-beta. Stimulation of FLS with IL-6 and IL-8 showed the increased concentrations of MMP-1, MMP-2 and MMP-3. CONCLUSION: Hypoxic environment of rheumatoid synovium might affect FLS to produce proinflammatory and proangiogenic cytokine such as IL-6 and IL-8. These cytokines again could stimulate MMPs production in FLS leading to joint destruction.

A case of pulmonary edema developed after intraarterial injection of iodinated contrast medium

Pulmonary edema is a rare adverse reaction to the iodinated contrast medium. Complaining of huge abdominal mass, a 52 years-old female was admitted to the Hangang Sungsim Hospital. On physical examination, the patient appeared to be healthy. She had stable vital Signs, i.e. BP: 120/80 mmHg, pulse rate: 80/min. etc. An adult head sized mass was palpated in the left mid and lower abdomen. Otherwise nonspecific. On laboratory studies, the positive findings were 8-10 WBC/HPF in urine, 25.6 mg/dl for BUN and PVC in EKG. It was negative for urine protein, serum creatinine and liver function test. We injected 100ml and 30 ml for Urografin 60 through the abdominal aortadividing 3 times and major branches of the abdominal aorta, respectively. Immediately after completing angiography, interstitial pulmonary edema was found, showing blurring of the vascular margins, perivascular haziness and thickening of the interiobular septal lines in the both lower lung fields. The blood pressure was dropped to 80/60 mmHg, but pulse rate was normal. She did not complian of dyspnea, and cyanosis was not developed. The urine volume was normally maintained. She was treated for pulmonary edema, which was completely absorbed after 20 hours. And the blood pressure was also normalized. We has experienced a case of pulmonary edema developed after intraarterial injection of the iodinated contrast medium without underlying cardiac, renal and hepatic problems, and reviewed the literatures on mechanisms of pulmonary edema caused by intravascular injection of the iodinated contrast materials.