No abstract available.
Interleukin 1 Receptor Antagonist Protein*

This study investigated the cytokines (IL-1alpha, IL-1beta, IL-1RA, TNF-alpha) mRNA expression in the early inflammatory process of alkali burned rabbit corneas. To create alkali burns, each 4 cornea of New Zealand White rabbits were exposed to filtering paper (5 mm diameter) treated with 1N NaOH for 1 minute at room temperature.e. Two unburned rabbits corneas were used as control. The mRNA levels for IL-1alpha, IL-1beta, IL-1RA, and TNF-alpha were monitored in corneas at 3, 6, 24, and 48 hours after alkali burn with semiquantative reverse transcription-polymerase chain reaction. Transcripts for IL-1alpha, IL-1beta, and TNF-alphawere expressed in 3 hours and increased through 48 hours, whereas those for IL-1betawas expressed in 3 hours and was not changed through 48 hours. IL-1alphamRNA level was detected lower than IL-1betamRNA in 3 hours but IL-1alphamRNA level was persist higher than IL-1betafrom 6 hours through 48 hours. IL-1RA mRNA level was expressed higher than others through 48 hours. These results indicate that IL-1 and TNF-alphalevel in the cornea are elevated during the early inflammatory process of alkali burn. IL-1alpha, IL-RA and TNF-alphamay play an important role in alkali-burned corneal inflammatory process.
Alkalies ; Burns ; Cornea* ; Cytokines ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-1* ; Rabbits* ; RNA* ; RNA, Messenger ; Tumor Necrosis Factor-alpha

OBJECTIVETo investigate the expression of the human interleukin-1 receptor antagonist (hIL-1ra) in the transfected chondrocytes of temporomandibular joint (TMJ).

METHODSChondrocytes of TMJ in vitro were transfected by hIL-1ra gene via cationic liposome as a medium. The stable transfected cells were selected by G418. The proliferations of the transduced cell were examined with the growth curve, cell population doubling time. The protein expressing in different periods was detected by immunocytochemistry and enzyme-linked immunosorbent assay (ELISA).

RESULTSThe proliferation suppression of gene transfected cells fell significantly with compared to normal cells. The expression of hIL-1ra was detected in the cell plasma and the cell culture supernatant. The highest expression of IL-1ra protein was at the time of 48 hours after gene transfection. The transiently transfected cells were secreted IL-1ra protein continuously 28 days and the stably transduced cells were secreted IL-1ra protein till 72 days.

CONCLUSIONThis study showed that hIL-1ra protein expressed positively in the cell plasma and the culture supernatant after gene transfection within a certain periods.

OBJECTIVE: Screw fixation via the paraspinal muscle sparing approach and by percutaneous screw fixation are known to diminish the risk of complications, such as, iatrogenic muscle injury as compared with the conventional midline approach. The purpose of this study was to evaluate tissue injury markers after these less traumatic screw fixation techniques for the treatment of L4-L5 spondylolisthesis. METHODS: Twenty-two patients scheduled for posterior lumbar interbody fusion (PLIF) at the L4-L5 segment for spondylolisthesis were prospectively studied. Patients were divided into two groups by screw fixation technique (Group I: paraspinal muscle sparing approach and Group II: percutaneous screw fixation). Levels of serum enzymes representing muscle injury (CK-MM and Troponin C type 2 fast), pro-inflammatory cytokine (IL-8), and anti-inflammatory cytokine (IL-1ra) were analyzed using ELISA techniques on the day of the surgery and 1, 3, and 7 days after the surgery. RESULTS: Serum CK-MM, Troponic C type 2 fast (TNNC2), and IL-1ra levels were significantly elevated in Group I on postoperative day 1 and 3, and returned to preoperative levels on postoperative day 7. No significant intergroup difference was found between IL-8 levels despite higher concentrations in Group I on postoperative day 1 and 3. CONCLUSION: This study shows that percutaneous screw fixation procedure is the preferable minimally invasive technique in terms of minimizing muscle injury associated with L4-L5 spondylolisthesis.
Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-8 ; Muscles ; Prospective Studies ; Spondylolisthesis ; Troponin C

BACKGROUND: Several lines of evidence suggest that host genetic factors influence the outcome of exposure to Mycobacterium tuberculosis. The aim of this study was to determine whether polymorphisms in interleukin-1beta (IL-1beta) and Interleukin-1 receptor antagonist (IL-1Ra) genes associate with the susceptibility or resistance to pulmonary tuberculosis in Korean. METHODS: IL-1beta and IL-1Ra gene polymorphism were investigated in 60 drug sensitive (DS) and 100 multidrug-resistant (MDR) pulmonary tuberculosis cases, and 96 healthy controls. IL-1beta-511/-31/+3954 and IL-1Ra genotype were determined by polymerase chain reaction. RESULTS: Allelic and genotypic frequencies of IL-1beta-511/-31/+3954 showed no significant difference in 3 groups. IL-1Ra allele 2 heterozygotes were less frequent in DS (p=0.03, OR=0.26, 95% CI 0.07 to 0.95) and MDR tuberculosis (p=0.008, OR=0.26, 95% CI 0.09 to 0.75) than controls, but there was no significant difference between DS and MDR tuberculosis (p=1.00). CONCLUSION: IL-1Ra allele 2 heterozygote may be associated with resistance to pulmonary tuberculosis in Korean. Further studies will be required to confirm whether these results are of biologic significance.
Alleles ; Genotype ; Heterozygote ; Humans ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-1* ; Interleukin-1beta* ; Mycobacterium tuberculosis ; Polymerase Chain Reaction ; Tuberculosis ; Tuberculosis, Multidrug-Resistant ; Tuberculosis, Pulmonary*

OBJECTIVES: The role of pro-inflammatory cytokines in the course of chronic otitis media with effusion (COME) has been documented. However, there are fewer studies on the action of anti-inflammatory cytokines in the middle ear. We sought determine whether there is an association between COME and anti-inflammatory cytokines and whether there are any differences in the cytokine profile in COME children with and without atopy. METHODS: Eighty-four children were divided into 3 groups: 32 nonatopic children with COME (group NA), 31 atopic children with COME (group A), and 21 children without COME and without atopy (control group C). Specimens from the middle ear were collected and evaluated by enzyme-linked immunosorbent assay for the cytokines interleukin-1 receptor antagonist (IL-1Ra) and immunoregulatory IL-10. RESULTS: Significantly higher IL-10 concentrations were found in both nonatopic and atopic children with COME compared to controls. No significant differences in IL-1Ra levels were found between atopic and nonatopic children with COME and the control group. CONCLUSION: We found no differences in the levels of IL-1Ra in atopic and nonatopic children with COME compared to controls. However, we found elevated IL-10 levels in the middle ear effusions from children with COME, with or without atopy. These elevated immunoregulatory cytokine levels suggest a role for new immunomodulatory treatments to prevent disease progression in COME, regardless of atopy.
Child* ; Cytokines ; Disease Progression ; Ear, Middle* ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-1* ; Interleukin-10* ; Otitis Media with Effusion* ; Otitis Media* ; Otitis*

BACKGROUND: The Fas antigen is a cell surface molecule that mediates apoptosis in many cell types. Matsues group indicated that keratinocytes constitutively express the Fas antigen and apoptosis was induced only on pretreatment with interferon-r (IFN-y) in cultured normal human keratinocytes (NHK). OBJECTIVE: We undertook this study to determine the induction of apoptosis by Fas antibody alone and/or in combination with IFN y, IL-1a in normal human keratinocytes (NHK) and transitional epithelioma cell lines (KB cell) which had lower levels of intracellular IL-1 receptor antago- nists (IL-1ra ). METHODS: We used cultured NHK and KB cells. Each cell was treated with IFN-r, IL-la and Fas antibody for induction of apoptosis. For quantifying the apoptosis, index fluorescent DNA- binding dyes were used. Result: Fas antibody alone could induce apoptosis not only in KB cells but also in NHK cells. The combination of Fas antibody and IFN-r enhanced the induction of apoptosis in NHK and KB cells. The IL-la alone could induce apoptosis only in KB cells which had relatively small amounts of IL-1ra compared to NHK. CONCLUSION: Our result may indicate that Fas antigen in human keratinocytes can regulate normal epidermal cellular differentiation and proliferation.
Antigens, CD95 ; Apoptosis* ; Carcinoma ; Cell Line ; Coloring Agents ; Humans* ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-1 ; Interleukin-1alpha ; KB Cells* ; Keratinocytes*

BACKGROUND: Chronic low grade inflammation is closely linked to type II diabetes, obesity, and atherosclerosis. Macrophages play a key role in the regulation of pro- or anti-inflammatory actions at the lesion sites of disease. Components of cordyceps militaris, cordycepin and adenosine, have been used for the modulation of inflammatory diseases. The effects of cordycepin in the modulation of macrophages have yet to be elucidated. We investigated the effects of cordycepin and adenosine on the morphological changes of macrophages under the inflammatory condition of LPS and an anti-inflammatory condition involving high concentrations of adenosine. METHODS: We confirmed the mRNA levels of the M1/M2 cytokine genes through RT-PCR and morphological change. RESULTS: LPS-activated macrophages returned to their inactivated original shape, i.e., they looked like naive macrophages, through the treatment with high concentrations of cordycepin (40 microgram/ml). LPS and adenosine activated macrophages also returned to their original inactivated shapes after cordycepin treatment; however, at relatively higher levels of cordycepin than adenosine. This change did not occur with relatively low concentrations of cordycepin. Adenosine down-regulated the gene expression of M1 cytokines (IL-1beta, TNF-alpha) and chemokines (CX3CR1, RANTES), as well as cordycepin. Additionally, M2 cytokines (IL-10, IL-1ra, TGF-beta) were up-regulated by both cordycepin and adenosine. CONCLUSION: Based on these observations, both cordycepin and adenosine regulated the phenotypic switch on macrophages and suggested that cordycepin and adenosine may potentially be used as immunomodulatory agents in the treatment of inflammatory disease.
Adenosine ; Atherosclerosis ; Chemokines ; Cordyceps ; Cytokines ; Deoxyadenosines ; Gene Expression ; Inflammation ; Interleukin 1 Receptor Antagonist Protein ; Macrophages ; Obesity ; RNA, Messenger

OBJECTIVE: To investigate the relationship between polymorphism in interleukin-1 receptor antagonist (IL-1ra) gene and bone mineral density (BMD) in postmenopausal Korean women. METHODS: The 86-base pair repeat polymorphism in the IL-1ra gene was examined by polymerase chain reaction (PCR) and electrophoresis in 285 postmenopausal Korean women. Serum bone alkaline phosphatase (BAP) and CrossLaps (CTX) were measured by immunoassay and BMD at the lumbar spine and proximal femur by dual energy X-ray absorptiometry. RESULTS: Four alleles in IL-1ra gene were identified; A1 (4 repeats), A2 (2 repeats), A3 (5 repeats), A4 (3 repeats). BMD at the lumbar spine, femoral neck, and trochanter in women carrying A2 allele was significantly lower, compared with noncarriage of that allele. Serum BAP levels in the former group were higher than those in the latter group, but no difference in serum CTX levels between two groups was observed. There were no differences in the distribution of IL-1ra A2 allele among normal, osteopenic, and osteoporotic postmenopausal women. CONCLUSIONS: BMD are associated with a polymorphism in IL-1ra gene in postmenopausal Korean women.
Absorptiometry, Photon ; Alkaline Phosphatase ; Alleles ; Bone Density* ; Electrophoresis ; Female ; Femur ; Femur Neck ; Humans ; Immunoassay ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-1* ; Polymerase Chain Reaction ; Spine

OBJECTIVE: IL-1beta is involved in the degradation of articular cartilage in various arthritides, including osteoarthritis (OA). Competitive inhibition of IL-1beta by IL-1 receptor antagonists (IL-1Ra) may represent a pathogenesis-based strategy for inhibiting degradation of the cartilage matrix. We investigated the hypothesis that controlled release of IL-1Ra using injectable, thermoreversible and complex coacervate combination gels as drug delivery systems might reduce matrix degradation in OA. METHODS: Thermoreversible combination gels that can be injected into joints were formed in aqueous solution by making a complex coacervate with recombinant human IL-1Ra (anakinra) and cationic macromolecules, and this was followed by co-formulation with methylcellulose as a negative thermosensitive polysaccharide. Gels containing anakinra were positioned in the upper insert of a transwell system and human OA chondrocytes were placed in the lower compartment and then they were stimulated with IL-1beta. The expression of matrix metalloproteinases (MMPs) was examined by performing real time PCR and ELISA. RESULTS: Complex coacervation between anakinra and protamine was successfully completed. IL-1Ra was released from the gels in a sustained release pattern for extended periods with minimal initial bursts. IL-1beta markedly enhanced the expression of MMP. The IL-1Ra released from the gels significantly inhibited the IL-1beta-induced MMP expression in the chondrocytes. CONCLUSION: We developed and optimized a novel injectable and thermoreversible gel system for the controlled release of IL-1Ra, and this drug delivery system effectively inhibited the IL-1beta-induced MMP expression of chondrocytes in a transwell system. Intra-articular local delivery of injectable and thermoreversible gels containing IL-1Ra into knees has the potential to provide prolonged therapy based on the pathophysiology of knee OA.
Arthritis ; Cartilage ; Cartilage, Articular ; Chondrocytes ; Drug Delivery Systems ; Gels ; Humans ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-1 ; Joints ; Knee ; Matrix Metalloproteinases ; Methylcellulose ; Osteoarthritis ; Real-Time Polymerase Chain Reaction