Biomedical subjects

Y Ohmoto

Publications and source records attributed to Y Ohmoto.

At least 19 recordsLinked to original sources

PubMed2001

In vitro inhibitory effects of Daphne oleoides ssp. oleoides on inflammatory cytokines and activity-guided isolation of active constituents.

Aerial parts of Daphne oleoides Schreber ssp. oleoides (Thymelaeaceae) are used to treat rheumatoid arthritis and lumbago in Turkish folk medicine. In order to evaluate folkloric utilization, in vitro inhibitory effects of the ethyl acetate extract and fractions obtained from this extract on interleukin 1 (IL-1alpha, IL-1beta) and tumour necrosis factor (TNF-alpha) biosynthesis were studied. Through chemical isolation techniques and activity-guided fractionation process, seventeen compounds were isolated and their structures were elucidated (numbered 1-17). Diterpenoids genkwadaphnin (3) and 1,2-dehydrodaphnetoxin (6) and a coumarin derivative daphnetin (9) showed potent inhibitory activity and were found to be the main active ingredients. Furthermore, gnidilatin (4), gnidilatin-20 palmitate (5), genkwadaphnin-20-palmitate (7) and gnidicin-20-palmitate (8), having diterpenoid structure, and eudesmine (12), wikstromol (13) and matairesinol (14), having lignan structure, were determined to possess moderate inhibitory activity and may have a contributory role in the effect of the remedy.

Acetates↗

PubMed2001

Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages.

BACKGROUND: Excessive lipid accumulation in macrophages plays an important role in the development of atherosclerosis. Recently, we discovered an adipocyte-specific plasma protein, adiponectin, that is decreased in patients with coronary artery disease. We previously demonstrated that adiponectin acts as a modulator for proinflammatory stimuli and inhibits monocyte adhesion to endothelial cells. The present study investigated the effects of adiponectin on lipid accumulation in human monocyte-derived macrophages. METHODS AND RESULTS: Human monocytes were differentiated into macrophages by incubation in human type AB serum for 7 days, and the effects of adiponectin were investigated at different time intervals. Treatment with physiological concentrations of adiponectin reduced intracellular cholesteryl ester content, as determined using the enzymatic, fluorometric method. The adiponectin-treated macrophages contained fewer lipid droplets stained by oil red O. Adiponectin suppressed the expression of the class A macrophage scavenger receptor (MSR) at both mRNA and protein levels by Northern and immunoblot analyses, respectively, without affecting the expression of CD36, which was quantified by flow cytometry. Adiponectin reduced the class A MSR promoter activity, as measured by luciferase reporter assay. Adiponectin treatment dose-dependently decreased class A MSR ligand binding and uptake activities. The mRNA level of lipoprotein lipase as a marker of macrophage differentiation was decreased by adiponectin treatment, but that of apolipoprotein E was not altered. Adiponectin was detected around macrophages in the human injured aorta by immunohistochemistry. CONCLUSIONS: The adipocyte-derived plasma protein adiponectin suppressed macrophage-to-foam cell transformation, suggesting that adiponectin may act as a modulator for macrophage-to-foam cell transformation.

Adipocytes↗

PubMed2001

B cell subsets in postmenopausal women and the effect of hormone replacement therapy.

OBJECTIVES: In elderly subjects the capacity for antibody production is depressed. This immunosenescence state of humoral immunity is associated with the occurrence of autoimmune disorders involving CD5+ B (B-1) cells. Since estrogen is capable of stimulating the production of autoantibodies, this sex steroid hormone may be a contributing cause of the higher incidence of autoimmune diseases in women. In the present study, B cell subsets in women during the postmenopausal period was determined. The effect of hormone replacement therapy (HRT) on B cell subsets was examined to establish whether the administration of gonadal hormones influence humoral immunity in postmenopausal women. METHODS: Forty six untreated pre- and postmenopausal women and 39 women on HRT were studied. The proportion of B-1 (CD5+) and conventional CD5- B (B-2) lymphocytes was determined by two-color flow cytometry. Serum autoantibodies to a nuclear antigen and to interleukin (IL)-1alpha were measured by immunofluorescence and by radioimmunoassay, respectively. Thirteen women were examined prospectively before and during HRT. RESULTS: In late postmenopausal women (> or = 30 years postmenopausal period), the proportion of B-2 cells was significantly reduced (p<0.01) compared to those of premenopausal and perimenopausal women. HRT induced a significant (p<0.01) increase in the percentage of B-2 cells, while that of B-1 cells remained unchanged. HRT did not affect autoantibody production. CONCLUSION: HRT may retard the progress of immunosenescence by increasing the production of B-2 cells. Moreover, HRT appears not to increase the risk of autoimmune diseases developing in postmenopausal women.

Adult↗

PubMed2001

Interferon-gamma-inducing activity of interleukin-18 in the joint with rheumatoid arthritis.

OBJECTIVE: To examine the levels of interleukin-18 (IL-18) bioactivity within the rheumatoid arthritis (RA) joint, and the differential effects of IL-12 and IL-18 on interferon-gamma (IFNgamma) production by T cell infiltrates. METHODS: Expression of IL-18 protein and messenger RNA (mRNA) was determined by enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction, respectively. The biologic activity of IL-18 was detected on the basis of IFNgamma secretion from IL-18-responding human myelomonocytic KG-1 cells. To determine the extent of inhibitory activity on binding of IL-18 to its receptor, a [125I]-IL-18 binding inhibition assay was performed, using a Chinese hamster ovary cell line transfected with a murine IL-18 receptor. RESULTS: The amount of IL-18 protein detected in both the serum and synovial fluid of RA patients was markedly larger than that detected in the serum and synovial fluid ofosteoarthritis (OA) patients, and serum IL-18 levels correlated with the levels of serum C-reactive protein. IFNgamma production by KG-1 cells was more strongly stimulated in synovial fluid samples from RA patients than in samples from OA patients, and this activity was largely diminished in the presence of anti-IL-18 antibody. In contrast, the activity of IL-18 binding inhibition in the serum and synovial fluid of RA patients was not significantly elevated compared with that in OA patients. RA synovial tissues showed increased expression of IL-18 mRNA and increased IL-18 protein synthesis compared with that in OA tissues. Purified CD14+ macrophages, but not activated fibroblast cell lines, from RA synovium were able to release mature IL-18, although both cell types expressed its transcripts. IL-18 alone showed a negligible effect on IFNgamma production by RA synovial tissue cells, in contrast to IL-12, which was directly stimulatory. However, IL-12-induced IFNgamma production was synergistically enhanced by IL-18, and yet was >50% reduced by neutralization of endogenous IL-18 with anti-IL-18 antibody. CONCLUSION: These results indicate that IL-18, produced predominantly by tissue macrophages, primarily potentiates IL-12-induced IFNgamma production by T cell infiltrates in RA synovium. Detection of significant IL-18 bioactivity in the joints, despite the presence of IL-18 binding inhibitors, supports an integral role of this cytokine in perpetuating the IFNgamma-dominant T cell cytokine response in RA.

Antibody Formation↗

PubMed2001

Interleukin 8 and vascular endothelial growth factor -- prognostic factors in human gastric carcinomas?

Gastric carcinoma cells express potent angiogenic factors including vascular endothelial growth factor (VEGF). We previously reported that interleukin-8 (IL-8) acts as an angiogenic factor for human gastric carcinomas. More recently, we found that IL-8 upregulates matrix metalloproteinase-9 (MMP-9) expression and increases invasive activity of gastric carcinoma cells. The purpose of this study was to determine whether the expression of IL-8 and VEGF correlates with clinicopathological parameters in human gastric carcinomas. IL-8 and VEGF expression levels were measured by an enzyme-linked immunosorbent assay (ELISA) in 56 gastric carcinomas and the surrounding normal mucosa. Macroscopic and histopathological tumour findings, presence of metastasis and prognosis were obtained from the patient records and endoscopic, surgical and pathological reports. IL-8 protein levels were higher in most neoplasms than in the corresponding normal mucosal tissue. In contrast, VEGF expression in the tumours was similar to that in normal mucosa. The IL-8 level in the neoplasms correlated significantly with the depth of invasion, venous invasion and lymphatic invasion. VEGF expression in the tumours correlated well with the depth of invasion and lymph node metastasis. No correlation between IL-8 and VEGF expression in the tumours was observed. The survival rates of patients with tumours displaying high IL-8 and VEGF expression levels were significantly lower (P<0.05) than those of patients with tumours displaying low IL-8 and VEGF expression. The results suggest that IL-8 and VEGF may be independent and important prognostic factors in human gastric carcinomas.

Adult↗

PubMed2001

Interleukin-6 production in lung tissue after transthoracic esophagectomy.

BACKGROUND: The mechanisms of the reported high increase in interleukin-6 (IL-6) levels after esophagectomy are unclear. We investigated the influence of an intrathoracic procedure, esophagectomy, on IL-6 production in lung tissue. STUDY DESIGN: Fourteen paired lung tissue samples were obtained from patients before and after they underwent transthoracic esophagectomy for esophageal cancer. IL-6 levels in the lung were measured with enzyme-linked immunosorbent assay, and IL-6 mRNA expression was determined with real-time quantitative reverse transcription-polymerase chain reaction. Immunohistochemical staining was used to localize IL-6, and circulating levels were also measured. RESULTS: IL-6 protein and mRNA were significantly increased in lung tissue after this intrathoracic procedure (p < 0.05). Peak levels of plasma IL-6 after surgery were correlated with IL-6 levels in lung tissues obtained after the procedure (p < 0.05). Immunohistochemical staining revealed IL-6 production from alveolar and bronchial epithelial cells but not from alveolar macrophages. CONCLUSIONS: Transthoracic esophagectomy causes an increase in IL-6 production from airway epithelial cells, secondary to increased expression of IL-6 mRNA. Local response of lung tissue may be one source of increased serum IL-6 after this procedure.

Aged↗

PubMed2001

Evaluation of two sperm antigens, rSMP-B and YWK-II, as targets for immunocontraception.

To determine whether sperm membrane components, rSMP-B and YWK-II, are suitable candidates as immunocontraceptives in humans, antifertility activities of the antibodies to the peptide fragments, rSMP-229 and rSMP-230 of rSMP-B and YAL-198 of YWK-II, were examined. In a previous report, anti-rSMP-230 antibody was shown to immobilise human sperm and to block human fertilisation, and the antigen (rSMP-230) to interact with antisperm antibodies found in sera of infertile women. Antibody to the second synthetic peptide, rSMP-229, corresponding to a different segment of rSMP-B, mimicked the biological activities of the anti-rSMP-230 antibody. Anti-YAL-198 antibody significantly, although weakly, inhibited human fertilisation. In the murine model, the anti-rSMP-B antibodies blocked in vitro fertilisation of mouse eggs but had no influence on embryo growth. Anti-YAL-198 antibody, however, arrested the growth of zygotes. In conclusion, rSMP-B, a human sperm protein, is a promising candidate in the development of an immunocontraceptive for human application. A second sperm protein, YWK-II, is effective as an antifertility immunogen in experimental animals.

Amyloid beta-Protein Precursor↗

PubMed2001

Immunosuppressive sesquiterpene alkaloids from Tripterygium wilfordii.

Nine new sesquiterpene pyridine alkaloids [wilfornines A (1), B (2), C (3), D (4), E (5), F (8), and G (9); wilfordinines I (6) and J (7)] and six known compounds (10-15) were isolated from a clinically used extract (T(II)) of Tripterygium wilfordii. The structures of 1-9 were elucidated by spectroscopic and chemical methods. The inhibitory effects on cytokine production of 1-3 and several related compounds were evaluated. Compounds 10 and 14 showed significant inhibitory effects on cytokine production.

Alkaloids↗

PubMed2001

Successful immunogene therapy using colon cancer cells (colon 26) transfected with plasmid vector containing mature interleukin-18 cDNA and the Igkappa leader sequence.

IL-18 is a novel cytokine that induces interferon (IFN)-gamma secretion and plays an important role in antitumor immunity. In the present study, we constructed plasmid vectors encoding the murine mature IL-18 cDNA linked with the Igkappa leader sequence and the pro-IL-18 cDNA to estimate the efficacy of the mature IL- 18 vector and to evaluate IL-18--producing tumor cells as a tumor vaccine. Colon 26 cells were transfected with the abovementioned vectors or with vector alone (mock). Reverse transcription-polymerase chain reaction analysis showed increased expression of murine IL-18 cDNA in both mature IL-18 and pro-IL-18 transfectants in comparison to that in mock transfected cells. The ability of the culture supernatants of mature IL-18 transfectants to induce IFN-gamma secretion was extremely high (40-140 pg/10(6) cells) in comparison to that of pro-IL-18 transfectants (4-18 pg/10(6) cells). When injected into syngeneic BALB/c mice, the growth of mature IL-18 transfectants, but not pro-IL-18 transfectants, was significantly less than that in mock transfected cells ( P< .01, by ANOVA and analysis of covariance). In addition, injection of colon 26 or Meth-A cells into mice immunized with a mature IL-18 transfectant revealed acquired immunity. Depletion of natural killer cells did not affect the growth of transfectants. However, the growth inhibitory effects were partially abrogated following treatment with anti-CD4+ and anti-CD8+ antibodies. These data suggest that the rejection of mature IL-18/colon 26 cells was mediated through T-cell activation. Gene therapy using mature IL-18 transfectants containing a plasmid vector and the Igkappa leader sequence may be a useful tumor vaccine.

Adenoviridae↗

PubMed2001

A neutrophil elastase inhibitor (ONO-5046) reduces neurologic damage after spinal cord injury in rats.

In view of a cytoprotective effect of elastase inhibitor on chemokine-mediated tissue injury, we examined the neuroprotective effect of ONO-5046, a specific inhibitor of neutrophil elastase, in rats with spinal cord injury. Standardized spinal cord compression markedly increased cytokine-induced neutrophil chemo-attractant (CINC)-1 mRNA and protein. Their increases correlated with neurologic severity of injured rats. Immunohistochemically, CINC-1 protein was detected sequentially in vascular endothelial cells at 4 h, in perivascular neutrophils at 8 h, and in neutrophils infiltrating into cord substance at 12 h. Pretreatment with ONO-5046 (50 mg/kg) markedly ameliorated motor disturbance in injured rats, and reduced CINC-1 protein and mRNA expression. ONO-5046 also significantly reduced the increase of neutrophil accumulation or infiltration estimated by myeloperoxidase activity, and the extent of vascular permeability by Evans blue extravasation in the injured cord segment in comparison to control animals receiving vehicle. These results suggest that CINC-1 contributed to inflammation in rat spinal cord injury and ONO-5046 attenuated neurologic damage partly by blocking CINC-1 production of the chemoattractant, preventing neutrophil activation and vascular endothelial cell injury.

Animals↗

PubMed2001

Postmenopausal changes in serum cytokine levels and hormone replacement therapy.

OBJECTIVE: Our purpose was to investigate the effect of hormone replacement therapy on the postmenopausal changes in serum cytokine levels. STUDY DESIGN: Fifteen cytokines were measured by an enzyme-linked immunosorbent assay in 97 untreated and hormone replacement-treated women. Thirteen women were examined before and during hormone replacement therapy. RESULTS: Serum concentrations of macrophage colony-stimulating factor were significantly (P < .05) lower during the early postmenopausal period (< or = 10 years) than the values in premenopause and the elevated levels in the late postmenopausal period (< or = 30 years). A significant increase in tumor necrosis factor alpha and a decline in transforming growth factor beta1 were found in late postmenopausal women. Serum levels of macrophage colony-stimulating factor in women receiving hormone replacement therapy were significantly higher than those in untreated postmenopausal women. Furthermore, hormone replacement therapy induced a significant (P < .01) increase in serum levels of macrophage colony-stimulating factor, whereas serum levels of other cytokines were not affected. CONCLUSION: It is well documented that macrophage colony-stimulating factor lowers serum cholesterol concentrations and prevents atherosclerosis. Inducing the production of macrophage colony-stimulating factor is a possible additional mechanism of hormone replacement therapy in mediating the antiatherogenic effect.

Adult↗

PubMed2001

Transient increase in the levels of T-helper 1 cytokines in postmenopausal women and the effects of hormone replacement therapy.

The aim of this study was to determine, at least in part, T-cell function in postmenopausal women and the effects of hormone replacement therapy (HRT). Levels of T-helper 1 (Th1) cytokines (IL-2 and IFN-gamma) and T-helper 2 (Th2) cytokines (IL-4 and IL-10) produced by phytohemagglutinin-stimulated whole blood cells from 72 untreated and 44 HRT-treated women were measured by ELISA. Thirteen of the 44 HRT-treated women were examined before and during HRT. The production of IL-2 increased gradually with advance of the postmenopausal period. The levels of IL-2 in women in the early (< or =10 years) and mid (>10 and <30 years) postmenopausal stages were significantly higher than those in women in their second, third and fourth decades. The level in women in the late (> or =30 years) postmenopausal stage, however, was significantly lower than those in women in the early and mid postmenopausal stages. The level of IFN-gamma was highest in women in the mid postmenopausal stage. On the other hand, the levels of Th2 cytokines did not change with age or after menopause until the mid postmenopausal period but were significantly lower in women in the late postmenopausal stage. IFN-gamma levels in women on HRT were significantly lower than those in untreated postmenopausal women at all postmenopausal stages. HRT induced a significant decrease in the production of IL-2 and IL-4. In conclusion, production of Th1 cytokines is augmented in women after menopause. HRT prevents this increase, thereby improving the aberration of Th1/Th2 balance that is implicated in an inadequate immune response and pathological conditions.

Adolescent↗

PubMed2000

Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway.

BACKGROUND: Among the many adipocyte-derived endocrine factors, we found an adipocyte-derived plasma protein, adiponectin, that was decreased in obesity. We recently demonstrated that adiponectin inhibited tumor necrosis factor-alpha (TNF-alpha)-induced expression of endothelial adhesion molecules and that plasma adiponectin level was reduced in patients with coronary artery disease (CIRCULATION: 1999;100:2473-2476). However, the intracellular signal by which adiponectin suppressed adhesion molecule expression was not elucidated. The present study investigated the mechanism of modulation for endothelial function by adiponectin. METHODS AND RESULTS: The interaction between adiponectin and human aortic endothelial cells (HAECs) was estimated by cell ELISA using biotinylated adiponectin. HAECs were preincubated for 18 hours with 50 microg/mL of adiponectin, then exposed to TNF-alpha (10 U/mL) or vehicle for the times indicated. NF-kappaB-DNA binding activity was determined by electrophoretic mobility shift assays. TNF-alpha-inducible phosphorylation signals were detected by immunoblotting. Adiponectin specifically bound to HAECs in a saturable manner and inhibited TNF-alpha-induced mRNA expression of monocyte adhesion molecules without affecting the interaction between TNF-alpha and its receptors. Adiponectin suppressed TNF-alpha-induced IkappaB-alpha phosphorylation and subsequent NF-kappaB activation without affecting other TNF-alpha-mediated phosphorylation signals, including Jun N-terminal kinase, p38 kinase, and Akt kinase. This inhibitory effect of adiponectin is accompanied by cAMP accumulation and is blocked by either adenylate cyclase inhibitor or protein kinase A (PKA) inhibitor. CONCLUSIONS: These observations raise the possibility that adiponectin, which is naturally present in the blood stream, modulates the inflammatory response of endothelial cells through cross talk between cAMP-PKA and NF-kappaB signaling pathways.

Adenylyl Cyclase Inhibitors↗

PubMed2000

Humoral immune responses to adenovirus vectors in the brain.

We have investigated the humoral immune response to E1-deleted adenovirus vectors encoding the lacZ gene introduced into the brains of mice. Injection of these non-replicating vectors into the brain induced systemic antibody production to adenovirus vectors in dose dependent manner. Apparent antibody production to beta-galactosidase, the product of the lacZ gene, was detected later than anti-adenovirus antibody. Neutralizing antibody was not detected. This study demonstrates that E1-deleted adenovirus vectors injected into the brain trigger humoral immune responses to the adenovirus and its gene products, but they are not sufficient to block the infection of cells by adenovirus upon repeat injection.

Adenoviridae↗

PubMed2000

Macrophage infiltration correlates with tumor stage and angiogenesis in human malignant melanoma: possible involvement of TNFalpha and IL-1alpha.

We examined whether macrophage infiltration is associated with angiogenesis in cutaneous melanoma. The numbers of macrophages and microvessels increased significantly with increasing depth of tumor and with tumor angiogenesis. Macrophage infiltration thus appeared to provide a useful diagnostic marker for the progression of cutaneous melanoma. We further examined whether human melanoma cells produce angiogenic factors in response to macrophage-derived cytokines, tumor necrosis factor alpha (TNFalpha) and interleukin-1 alpha (IL-1alpha). Treatment of melanoma cells with TNFalpha and IL-1alpha in vitro enhanced the production of interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF), and of basic fibroblast growth factor (bFGF) to a lesser degree, in human melanoma cells. Lipopolysaccharide (LPS)-activated human monocytes enhanced production of IL-8, VEGF, TNF alpha, as well as IL-1alpha, but not bFGF. Co-culture of human monocytes and human melanoma cells was also found to significantly enhance production of IL-8 and VEGF in the absence and presence of LPS, compared with either monocytes or melanoma cells alone. The production of IL-8 and VEGF from co-cultured melanoma cells and LPS-activated monocytes was blocked when anti-TNF-alpha antibody or anti-IL-1alpha antibody was co-administrated. This is direct evidence that production of the potent angiogenic factors IL-8 and VEGF from melanoma cells is up-regulated through TNFalpha and/or IL-1alpha secreted by activated monocytes/macrophages, influencing both tumor growth and angiogenesis in melanomas.

Adult↗

PubMed2000

Allergen-induced mRNA expression of IL-5, but not of IL-4 and IFN-gamma, in peripheral blood mononuclear cells is a key feature of clinical manifestation of seasonal allergic rhinitis.

OBJECTIVES: To investigate the allergen-induced messenger RNA (mRNA) expression of interleukin (IL) 4, IL-5 and interferon gamma (IFN-gamma) in peripheral blood mononuclear cells from individuals sensitized by Japanese cedar (Cryptomeria japonica) pollens, and to elucidate the clinical role of IL-4, IL-5, and IFN-gamma in the allergen sensitization and clinical manifestation of allergic disorders. DESIGN: This study included 30 patients sensitized to the pollen and 14 nonatopic healthy volunteers. Peripheral blood mononuclear cells (1.0 x 10(6) cells/mL) of each individual were cultured at 37 degrees C for 24 hours in the presence of 10 microg/mL of Cry j 1, a major allergen of the pollens. Total cellular RNA was extracted from the peripheral blood mononuclear cells, and IL-4, IL-5, and IFN-gamma mRNA expression was determined with a reverse transcriptase polymerase chain reaction. RESULTS: From the results of a survey of symptom diary cards and interviews regarding nasal symptoms during the pollen season in 1998, we found that 20 patients (symptomatic group), but not 10 patients (asymptomatic group), had typical symptoms of seasonal allergic rhinitis. Interleukin 4 mRNA was not expressed in the nonatopic subjects but was expressed in 9 asymptomatic patients and in 17 symptomatic patients. Interleukin 5 mRNA was exclusively expressed in the symptomatic patients. Interferon gamma mRNA expression did not differ significantly among the nonatopic subjects, asymptomatic patients, and symptomatic patients. CONCLUSIONS: This study has clearly highlighted an interesting and new concept that IL-4 is implicated in allergen sensitization but not in clinical manifestation, and that IL-5 may not be a feature of atopy in itself but seems to be a hallmark of clinical manifestation of ongoing atopic diseases.

Adolescent↗

PubMed2000

Triterpenoids from Tripterygium wilfordii.

The extract (T(II)) of Tripterygium wilfordii Hook f. afforded four triterpenoids: wilforic acid D (3beta,24-epoxy-2alpha-hydroxy-24R*-ethoxy-29-friedelanoic acid); (E) 3beta,24-epoxy-2-oxo-3alpha-hydroxy-29-friedelanoic acid; (F) 2beta-hydroxy-3-oxo-friedelan-29-oic acid; 29-hydroxy-3-oxo-olean-12-en-28-oic acid and 17 known triterpenoids. Their structures were established on the basis of spectroscopic studies. In a bioactivity analysis, only the known dulcioic acid compound showed a significant inhibitory effect on cytokine production.

Immunosuppressive Agents↗

PubMed2000

Thyroid hormones influence serum leptin levels in patients with Graves' disease during suppression of beta-adrenergic receptors.

Leptin is a protein product of the ob gene, mainly produced by adipocytes. Leptin is thought to play an important role in the homeostasis of body weight by suppressing appetite and increasing energy consumption. The aim of this study was to investigate the possible effect of thyroid hormone on the regulation of the leptin system during suppression of beta-adrenergic receptors in Graves' patients. We studied 15 adult female patients with Graves' disease. Thyroid function, serum levels of leptin, and percent body fat (%BF) were examined at four different clinical conditions during therapy (A, untreated; B, beta-adrenergic antagonist only [A, B; hyperthyroid], C, beta-adrenergic antagonist and antithyroid drug; D, antithyroid drug only [C, D; euthyroid]). The use of beta-adrenergic antagonist significantly reduced heart rate in spite of hyperthyroid state, indicating sufficient suppression of beta-adrenergic receptors. During treatment with beta-adrenergic antagonist, leptin percentage of body fat (%BF) ratio significantly decreased in euthyroid state compared to that in hyperthyroid state (from 38.7 +/- 21.3 to 18.1 +/- 19.3, p = 0.003). Moreover, there was a significantly positive correlation between delta leptin/%BF and delta free thyroxine (FT4) (r = 0.51, p = 0.008). Under a euthyroid state induced by antithyroid drug treatment, leptin/%BF did not change in spite of withdrawal of beta-adrenergic antagonist. Our data indicate that thyroid hormones could increase serum leptin level during suppression of beta-adrenergic receptors in Graves' patients. Our data also suggest that the beta-adrenergic action of thyroid hormones might be partly mediated by regulation of leptin.

Adrenergic beta-Antagonists↗