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R A Ajjan

Publications and source records attributed to R A Ajjan.

At least 19 recordsLinked to original sources
PubMed2001

Once versus divided daily dosing with delayed-release mesalazine: a study of tissue drug concentrations and standard pharmacokinetic parameters.

BACKGROUND: Delayed-release mesalazine is traditionally taken as three divided doses. However, it is well-recognized that dosing frequency has a significant impact on compliance and that once daily dosing is preferable. METHODS: We measured serum, urinary, faecal and rectal tissue concentrations of 5-aminosalicylic acid and N-acetyl 5-aminosalicylic acid in 24 healthy volunteers following dosing with delayed-release mesalazine, 1.2 g or 2.4 g daily, given as either a single daily dose at 08:00 hours or in three divided doses at 08:00, 13:00 and 18:00 hours. RESULTS: Urinary and faecal excretion and rectal tissue concentrations of 5-aminosalicylic acid and N-acetyl 5-aminosalicylic acid were similar following single or divided daily dosing, at both doses studied. Peak serum concentrations were found at 06:00-09:00 following divided dosing and at 17:00-20:00 following once daily dosing. However, peak and trough serum levels and serum area under curve values (AUC) were similar with both regimens and at both doses. CONCLUSIONS: Urinary, faecal and rectal tissue concentrations are similar following single or divided daily dosing. Minor differences in serum levels were apparent but maximum, minimum and AUC values were similar. Clinical trials should examine the efficacy and toxicity of once daily dosing in patients with ulcerative colitis.

Adolescent↗
PubMed2000

The role of T-helper cytokines in human reproduction.

OBJECTIVE: To explore the role of maternal periimplantation endometrial T-helper-1 (TH-1) and T-helper-2 (TH-2) cytokines in the success or failure of human reproduction and their relation to the endocrine system and subsequent pregnancy outcome. DESIGN: Controlled, prospective study. SETTING: A tertiary care hospital with a university-based reproductive medicine clinic. PATIENT(S): Healthy women and women with recurrent miscarriage who had no history of infertility or autoimmune disease. INTERVENTION(S): Measurement of qualitative cytokine expression by RT-PCR and quantitative by ELISA, also hormone levels and pregnancy outcome. MAIN OUTCOME MEASURE(S): Expression of TH-1 and TH-2 cytokines and correlation with hormone levels and subsequent pregnancy outcome. RESULT(S): Levels of TH-1 cytokines were significantly greater and higher in women with recurrent miscarriage compared with controls, whereas levels of TH-2 cytokine interleukin-6 were significantly lower in women with recurrent miscarriage than in controls. There was no correlation between cytokine expression and serum hormone levels, and periimplantation cytokine levels were not predictive of subsequent pregnancy outcome in women with recurrent miscarriage. CONCLUSION(S): This study demonstrated in vivo that women with recurrent miscarriage exhibit primarily TH-1 cytokines, whereas healthy women exhibit decreased TH-1 cytokines and increased TH-2 cytokines. This suggests a potential role for a dichotomous T-helper response in the mediation of subsequent reproductive events. This maternal T-helper response appears to operate independently of hormonal factors in influencing the success or failure of human reproduction, as no correlation was evident between serum hormone levels and cytokine levels. An attempt to use periimplantation TH-1 and TH-2 cytokine profiles as a predictor of subsequent pregnancy outcome (live birth or no live birth) was limited by the small number of patients studied.

Abortion, Habitual↗
PubMed2000

Dose loading with delayed-release mesalazine: a study of tissue drug concentrations and standard pharmacokinetic parameters.

AIMS: Tissue concentrations of 5-aminosalicylic acid (5ASA) and its metabolites may influence the clinical course of inflammatory bowel disease. Since the factors that determine tissue drug concentrations are unknown we have studied the relationships between the oral dose of delayed-release mesalazine, rectal tissue drug concentrations and standard pharmacokinetic parameters. METHODS: Twelve healthy volunteers were studied following 7 days treatment with 1.2, 2.4 and 4.8 g of delayed-release mesalazine daily. 5-aminosalicylic acid and N-acetyl 5-aminosalicylic acid concentrations were measured in serum, urine, stool and rectal tissue biopsies. RESULTS: Serum concentrations and 24 h urinary excretion of 5ASA and N-acetyl 5ASA increased as the oral dose of mesalazine was increased from 1.2 g through 2.4 g to 4.8 g daily (serum area under curve (AUC):5ASA = 3. 9, 15.4 and 46.8 microg ml-1 h, P < 0.0001; N-acetyl 5ASA = 17.2, 30. 9 and 57.8 microg ml-1 h, P < 0.0001: urinary excretion: 5ASA = 1.8, 85.5 and 445 mg, P < 0.0001; N-acetyl 5ASA = 250, 524 and 1468 mg, P < 0.0001, respectively). Faecal 5ASA excretion increased as the oral dose increased from 1.2 g to 2.4 g but did not increase further with 4.8 g daily dosing whereas faecal N-acetyl 5ASA excretion was similar at all three doses. Rectal tissue concentrations of 5ASA increased markedly, and N-acetyl 5ASA increased modestly, as the dose of oral mesalazine increased from 1.2 g to 2.4 g daily but neither increased further with 4.8 g daily dosing. CONCLUSIONS: The relationship between the ingested dose of delayed-release mesalazine and rectal tissue drug concentrations is complex. Factors other than dose are likely to be important determinants of rectal tissue drug concentrations.

Adolescent↗
PubMed2000

Tissue iodine content and serum-mediated 125I uptake-blocking activity in breast cancer.

In the thyroid, active transport of iodide is under control of the TSH-dependent Na+/I- symporter (NIS), whereas in the breast such control is less well understood. In this study, NIS expression was demonstrated by RT-PCR in 2 of 2 fibroadenomata and 6 of 7 breast carcinoma messenger ribonucleic acid isolates. In addition, mean total tissue iodine levels of 80.9 +/- 9.5 ng I/mg protein in 23 benign tumors (fibroadenomata) were significantly higher than those in 19 breast cancers taken from either the tumor (18.2 +/- 4.6 ng I/mg) or morphologically normal tissue taken from within the tumor-bearing breast (31.8 +/- 4.9 ng I/mg; P < 0.05 in each case). Inhibition of 125I uptake into NIS-transfected CHO cells was observed in serum from 20 of 105 (19.0%) breast carcinoma, 8 of 49 (16.3%) benign breast disease, and 27 of 86 (31.4%) Graves' patients, but in only 1 of 33 (3.0%) age-matched female controls. IgG purified from serum of patients showing positive 125I uptake inhibition also inhibited iodide uptake, suggesting that such inhibition was antibody mediated. 125I uptake inhibition was significantly associated with thyroid peroxidase antibody positivity (P < 0.05) in sera from breast cancer patients, but not in those with benign breast disease, once again suggesting an association between thyroid autoimmunity and breast carcinoma.

Animals↗
PubMed2000

Detection of binding and blocking autoantibodies to the human sodium-iodide symporter in patients with autoimmune thyroid disease.

The sodium iodide symporter (NIS) is a novel autoantigen in autoimmune thyroid disease (ATD). A recent study has described the development of a bioassay for human (h) NIS antibody detection, but this will not detect antibodies that bind the symporter without modulating its activity. Therefore, the establishment of a binding assay is of importance to determine the overall prevalence of hNIS antibodies in ATD patients. An in vitro transcription and translation system was used to produce [35S]-labeled hNIS. The radiolabeled ligand reacted specifically in immunoprecipitation experiments with rabbit antiserum raised against a peptide fragment of hNIS. Subsequently, the reactivity of control and ATD sera to translated [35S]hNIS was determined using RIAs. A significant difference in the frequency of hNIS antibody-positive sera was found when patients with either Graves' disease (GD) or autoimmune hypothyroidism (AH) were compared with normal controls (P = 0.01 and P = 0.03, respectively). Of 49 GD and 29 AH sera tested, 11 (22%) and 7 (24%), respectively, were found to contain hNIS antibodies. Differences were also significant when the antibody-binding indices of the control group of sera were compared with those of both the GD and the AH patient sera (P < 0.0001 and P = 0.001, respectively). In contrast, sera from 10 patients with Addison's disease and 10 patients with vitiligo (without associated ATD) were all negative for antibody reactivity to the symporter. No differences were detected when the antibody binding indices of either the Addison's disease or the vitiligo sera were compared with those of the normal sera group (P = 0.9 and P = 0.6, respectively). Eight of the 11 (73%) GD and 3 of the 7 (43%) AH sera, which were positive for hNIS antibodies in the immunoprecipitation assay, were also found to inhibit iodide uptake in hNIS-transfected CHO-K1 cells, suggesting the existence of antibodies in some serum samples that bind to the symporter without modulating its function. Overall, a significant correlation was found between the iodide uptake inhibition and the binding assays for hNIS antibody detection (r = 0.49, P < 0.0001). In summary, we have developed a specific and quantitative assay for the detection of hNIS binding antibodies in sera of patients with ATD. This system offers the advantage of studying antibody reactivity against conformational epitopes and will be useful in understanding the role of NIS autoreactivity in the pathogenesis of ATD.

Addison Disease↗
PubMed1999

Analysis of a microsatellite polymorphism of the cytotoxic T-lymphocyte antigen-4 gene in patients with vitiligo.

The CTLA-4 gene encodes a T-cell receptor that is involved in the regulation of T-cell activation. Recent studies have demonstrated an association of a microsatellite polymorphism [variant lengths of a dinucleotide (AT)n repeat] lying in exon 3 of the CTLA-4 gene, specifically a 106-bp allele, with autoimmune disorders, such as Graves' disease, autoimmune Addison's disease and autoimmune hypothyroidism. The aim of the present study was to determine whether the same polymorphism of the CTLA-4 gene was associated with vitiligo, a disorder that may have an autoimmune origin and can be present in patients who have one or more autoimmune diseases. CTLA-4 gene microsatellite polymorphisms were determined for 74 vitiligo patients (53 without any autoimmune disorder; 21 with one or more autoimmune disease) and 173 healthy controls, who had no clinical evidence of either vitiligo or any other autoimmune disorder, by polymerase chain reaction amplification of genomic DNA and resolution of the products on polyacrylamide sequencing gels. The frequency of the 106-bp allele was significantly increased (chi2 = 5. 2; P = 0.02) in vitiligo patients as a whole, in comparison with control subjects. However, when the patients were classified according to the absence or presence of an autoimmune disorder, the frequency of the 106-bp allele was significantly increased (chi2 = 14.8; P = 0.0001) only in the group of vitiligo patients who also had an autoimmune disease. However, the fact that 17 of 21 patients also had either autoimmune thyroiditis or autoimmune Addison's disease probably accounts for the apparent association of vitiligo and the 106-bp allele in this patient group. However, it was found that the relative risk of 3.2, conferred by the 106-bp allele in this group of vitiligo patients, was greater than that found for patients with only either Graves' disease, autoimmune hypothyroidism or autoimmune Addison's disease, with values of 2.1, 2.2 and 2.2, respectively. For the group of patients without an autoimmune disorder, there was no significant difference (chi2 = 0.2; P = 0.64) in the frequency of the 106-bp allele when compared with control subjects. These results indicate that there is no association between the 106-bp allele and vitiligo, at least when the disorder occurs in the absence of an autoimmune disease.

Abatacept↗
PubMed1998

Simple method for the determination of 5-aminosalicylic and N-acetyl-5-aminosalicylic acid in rectal tissue biopsies.

We describe a sensitive high-performance liquid chromatographic method for the determination of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid in rectal tissue biopsies. Samples were derivatised using propionic anhydride and proteins were precipitated with methanol. A Supelcosil ABZ column (150x4.6 mm I.D., 5 microm silica particles) was used with a mobile phase comprising 0.1 M acetic acid, acetonitrile and triethylamine (1600:114:6, v/v/v). Fluorescence detection was employed and detection limits were 0.2 ng/mg tissue at a signal-to-noise ratio of three (measured concentration: 5-aminosalicylic acid, 0.254 (0.228-0.286) ng/mg, C.V. 10.7%; N-acetyl-5-aminosalicylic acid, 0.18 (0.154-0.198) ng/mg, C.V 9.8%). This assay was validated for use with serum, urine and faecal samples for which it proved to be both precise and accurate (C.V.<10%, measured concentration within 10%).

Aminosalicylic Acids↗
PubMed1998

Mesalazine release from a pH dependent formulation: effects of omeprazole and lactulose co-administration.

AIMS: Delayed-release formulations of mesalazine often rely on the gastrointestinal luminal pH profile to deliver 5-aminosalicylic acid (5ASA) to the colon. The aim of this study was to examine the influence of luminal pH on mesalazine release. METHODS: We studied the effect of co-administration of omeprazole and lactulose on the steady-state pharmacokinetics of Eudragit S-coated mesalazine in healthy volunteers. RESULTS: No significant changes in urinary or faecal levels of 5ASA or its main metabolite, N-acetyl 5ASA, were apparent. CONCLUSIONS: This study suggests that co-administration of omeprazole and lactulose does not impair the release of delayed-release mesalazine.

Adolescent↗
PubMed1998

Regulation and tissue distribution of the human sodium iodide symporter gene.

OBJECTIVE: Iodide uptake by the thyroid gland is mediated by the sodium iodide symporter (NIS). In the present report, we have analysed the factors that modulate human NIS mRNA expression and iodide uptake in primary thyroid follicular cell (TFC) cultures. In addition, NIS mRNA tissue distribution was investigated. METHODS: Primary thyroid follicular cell cultures were treated with human recombinant TSH with or without cytokines for 72 h. Subsequently, NIS gene expression and iodide uptake were analysed using reverse transcription-polymerase chain reaction (RT-PCR) and 125I uptake, respectively. Human tissue samples were investigated for NIS gene expression using both RT-PCR and Northern blotting. RESULTS: Human TSH increased both NIS gene expression and iodide uptake in TFC cultures in a dose-dependent manner. Using concentrations of 0.1 U/l of hTSH, a minor increase in NIS gene expression was detected without a detectable increase in iodide uptake. IL-1 alpha, TNF alpha and IFN gamma at concentrations of 10(5) U/l all inhibited TSH-induced NIS gene expression and iodide uptake. In these experiments, there was a good correlation between NIS mRNA expression and iodide uptake. Using RT-PCR higher levels of NIS mRNA were detected in Graves' disease (GD) compared to multi-nodular goitre tissue samples. Stomach and salivary gland tissue also expressed NIS mRNA, whereas low levels were found in the mammary gland and extraocular muscle tissue. No expression was detected in the ovary, oesophagus, colon, extraocular fat or skin. In contrast, Northern blot analysis failed to detect NIS in stomach, salivary gland, intestinal fat or non-toxic multi-nodular goitre tissue samples, although this was present in GD thyroid tissue. CONCLUSION: TSH upregulates sodium iodide symporter gene expression and iodide uptake in primary thyroid follicular cell cultures, and this induction is modulated by cytokines. Variable levels of sodium iodide symporter mRNA are present in different tissue samples, with high expression evident in Graves' disease thyroid tissue.

Actins↗
PubMed1998

A cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism is associated with autoimmune Addison's disease in English patients.

OBJECTIVE: Recent studies have demonstrated an association between a microsatellite polymorphism of the CTLA-4 gene, specifically a 106 base pair allele, and both Graves' disease and autoimmune hypothyroidism. The aim of the present study was to determine whether the same polymorphism of the CTLA-4 gene was associated with autoimmune Addison's disease. DESIGN AND PATIENTS: We analysed a microsatellite polymorphism (variant lengths of a dinucleotide (AT)n repeat) within exon 3 of the CTLA-4 gene in the following groups: 21 English patients with non-associated Addison's disease, 18 with autoimmune polyglandular syndrome type 2 (APS2) and 173 healthy control subjects; 26 Norwegian patients with non-associated Addison's disease, 9 with autoimmune polyglandular syndrome type 1 (APS1), 17 with APS2 and 100 controls; 3 Finnish patients with non-associated Addison's disease, 5 with APS2 and 71 controls; 10 Estonian patients with non-associated Addison's disease, 2 with APS2 and 45 controls. MEASUREMENTS: The CTLA-4 microsatellite gene polymorphisms were determined by polymerase chain reaction amplification of genomic DNA and resolution of the products on sequencing gels. RESULTS: The frequency of the 106 base pair allele was significantly increased in the groups of English patients with either non-associated Addison's disease or APS2 (P = 0.02 and 0.04, respectively), when compared to healthy controls with no clinical evidence or family history of either Addison's disease or any other autoimmune disorder. For Norwegian patients with either non-associated Addison's disease, APS1 or APS2, there was no association (P = 0.69, 0.62 and 0.97, respectively). This was also the case for Finnish patients with either non-associated Addison's disease or APS2 (P = 0.23 and 0.28, respectively) and for Estonian patients with either non-associated Addison's disease or APS2 (P = 0.34 and 0.29, respectively). CONCLUSIONS: These results indicate that differences exist in the frequency of the 106 base pair allele in different population groups and in only the English population was the 106 base pair allele associated with Addison's disease.

Abatacept↗
PubMed1998

A new chemiluminescent assay for the rapid detection of thyroid stimulating antibodies in Graves' disease.

OBJECTIVE: Thyroid stimulating antibodies (TSAb) are the cause of Graves' disease (GD). At present, these antibodies can only be measured using bioassays, which are generally time consuming and difficult to apply to whole serum. Here we describe a new chemiluminescent assay for the detection of TSAb in serum samples. METHODS: A Chinese hamster ovary (CHO) cell line, stably transformed with a reporter plasmid containing the firefly luciferase gene under the transcriptional control of multiple cAMP responsive elements (CRE), was transfected with the human thyroid stimulating hormone (TSH) receptor. A clonal cell line, (NA-4), was obtained which showed a dose-dependent increase in luciferase activity in response to bovine and human TSH stimulation. NA-4 was subsequently used to study TSAb activity in 42 GD sera. RESULTS: Of the GD sera 25 (60%) produced an increase in luciferase activity of 1.4-9 fold that obtained with control sera. Results were compared with an established bioassay for TSAb, based on the direct measurement of intracellular cAMP, and there was a significant correlation between the two assays (r = 0.8; P < 0.0001). IgG from GD patients, but not controls, also increased luciferase activity in NA-4 cells using concentrations as low as 3 mg/l in selected samples. CONCLUSION: The present report describes a simple, sensitive and rapid assay for the detection of TSAb, with application both in the clinical analysis of GD patient sera and as a potential research tool for use in the isolation of TSAb monoclonal antibodies.

Animals↗
PubMed1998

Profile of cytokine mRNA expression in peri-implantation human endometrium.

The human embryo and subsequent fetus is a semi-allograft and immunologically foreign to the mother. Successful embryonic implantation and maintenance of normal pregnancy depends on intricate interactions between the invading embryo, maternal endometrium and maternal immune response. Cytokines are pivotal in determining the type of maternal T-helper immune response, which can be divided into T-helper 1 (TH1)-mediated delayed hypersensitivity and T-helper 2 (TH2)-mediated humoral immunity. We examined the pattern of TH1 [interleukin (IL)-2, IL-12 and interferon-gamma] and TH2 (IL-4 and IL-6) cytokine expression in the peri-implantation endometrium of 10 fertile, multiparous women. Endometrial samples were timed to the mid-cycle luteinizing hormone (LH) surge, with collection on days LH+7 to LH+9. Analysis for cytokine mRNA was by mRNA extraction and reverse transcription-polymerase chain reaction. The results show a lack of TH1 and predominant TH2 cytokine expression. We postulate that endometrial cytokines may contribute to the local modulation of maternal adaptive immune response in peri-implantation endometrium, to facilitate successful embryonic implantation and maintenance of pregnancy.

Adult↗
PubMed1998

Analysis of the T-cell receptor Valpha repertoire and cytokine gene expression in Sjögren's syndrome.

The antigen receptor diversity of pathogenic T cells in Sjögren's syndrome (SS) may have important implications in the development of the disease; cytokines from these cells and other sources also play a role in the pathogenesis of this disease. Using a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) technique, we have attempted to correlate the presence of restriction in the T-cell receptor (TCR) repertoire with cytokine profiles. We have analysed TCR V alpha family usage, and the expression of interleukin-1alpha (IL-1alpha), IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), in labial biopsies from 12 patients with SS and compared these with samples from three patients with chronic sialadenitis (CS). Only one of the SS biopsies showed evidence of V alpha restriction (three out of 18 gene families). Apart from this, expression patterns were similar in both patient groups. Four of the 12 SS samples demonstrated a 'limited heterogeneity' of the V alpha repertoire with 3-4 families predominantly expressed, in particular V alpha1 and V alpha3. Peripheral blood lymphocytes were unrestricted. The cytokine profiles of the SS and CS biopsies were generally similar. However both IFN-gamma and IL-1alpha were absent from CS, but present in SS samples. The expression of IFN-gamma in the majority of the samples, together with a lack of IL-4 and IL-13 mRNA, suggests the predominance of a Th1 response in SS. There was no clear association between the repertoire of V alpha genes expressed and the cytokine profile observed. However, the V alpha restriction in one SS sample did correspond with a limited diversity of cytokines detected.

Adult↗
PubMed1998

The modulation of the human sodium iodide symporter activity by Graves' disease sera.

The transport of iodide into the thyroid, catalyzed by the Na+/I- symporter (NIS), is the initial and rate-limiting step in the formation of thyroid hormones. To study the basic characteristics of the human (h) NIS, we have established a Chinese hamster ovary cell line stably expressing the hNIS (CHO-NIS9). In agreement with previous work on the rat NIS, iodide uptake in these cells was initiated within 2 min of the addition of 131I, reaching a plateau after 30 min. Both perchlorate and thiocyanate inhibited iodide uptake in a dose-dependent manner, with inhibition evident at concentrations of 0.01 and 0.1 micromol/L, respectively, and reaching complete inhibition at 20 micromol/L and 500 micromol/L, respectively. Ouabain, which blocks the activity of the Na+/K+ adenosine triphosphatase, also inhibited iodide uptake in a dose-dependent manner, starting at concentrations of 100 micromol/L and reaching maximum inhibition at 1600 micromol/L, indicating that iodide uptake in these cells is sodium dependent. CHO-NIS9 cells were further used to study 88 sera from patients with Graves' disease, for iodide uptake inhibitory activity, which were compared with sera from 31 controls. Significant iodide uptake inhibition was taken as any inhibition in excess of the mean + 3 SD of the results with the control sera. On this basis, 27 (30.7%) of the Graves' sera, but none of the controls, inhibited iodide uptake in CHO-NIS9. IgGs from these patients also inhibited iodide uptake, indicating that this inhibitory activity was antibody mediated. In summary, we have established a CHO cell line stably expressing the hNIS and shown that antibodies in GD sera can inhibit iodide uptake in these cells. This further emphasizes the role of NIS as a novel autoantigen in thyroid immunity.

Animals↗
PubMed1998

The sodium iodide symporter gene and its regulation by cytokines found in autoimmunity.

Iodide concentration by the thyroid gland, an essential step for thyroid hormone synthesis, is mediated by the Na+/I- symporter (NIS). To identify factors that may regulate this process, we have studied NIS gene expression in the Fisher rat thyroid cell line (FRTL-5) by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) technique. Increasing concentrations of bovine TSH (0.1, 1, 10, 50 and 100 mU/l), with or without tumour necrosis factor-alpha (TNF alpha), interferon-gamma (IFN gamma) or interleukin-1 alpha (IL-1 alpha) were added to FRTL-5 cells previously deprived of TSH for a minimum of 5 days. RNA was extracted and samples were studied for NIS expression. TSH enhanced NIS mRNA expression in a dose-dependent manner, with induction evident at 0.1 mU/l, reaching a peak at 50 mU/l, an effect detected after 6 h of stimulation, but not in the first 2 h. Both TNF alpha and, to a lesser extent, IL-1 alpha inhibited basal and TSH-induced NIS expression. High concentrations of IFN gamma also downregulated TSH-stimulated NIS mRNA expression. Using the same technique, we also investigated NIS mRNA tissue distribution in two male and one female Wistar rats. High levels of NIS expression were detected in the thyroid, stomach, and mammary gland, lower levels were found in the intestine, adipose tissue and liver, borderline levels were expressed in the salivary gland, and no expression was detected in the kidneys. In summary, we have shown that TSH upregulates rat NIS gene expression in vitro, and this induction can be modulated by cytokines. Analysis of the distribution of rat NIS mRNA ex vivo demonstrated variable levels of NIS transcription in different tissue samples.

Adipose Tissue↗
PubMed1997

Cytokines and Graves' disease.

Cytokines are an extraordinarily diverse group of molecules, with pleiotropic and often overlapping effects. They are crucial to the autoimmune response, and, in particular, regulation of CD4+ and CD8+ T-cell function depends on the balance of cytokines produced during an immune response. It is also now clear that cytokines are produced by a wide array of cells, including the thyroid follicular cells (TFCs). Intrathyroidal lymphocytes produce a heterogeneous pattern of cytokines and we have summarized the likely effects of these. In Graves' disease, TFCs can themselves express immunologically important molecules as the result of cytokine stimulation and these could contribute to the perpetuation of the autoimmune process. In addition, cytokines have a number of generally inhibitory effects on thyroid hormone production which would tend to counter the stimulatory effects of thyroid-stimulating hormone receptor antibodies in Graves' disease.

Antibody Formation↗
PubMed1997

Detection of IL-12, IL-13, and IL-15 messenger ribonucleic acid in the thyroid of patients with autoimmune thyroid disease.

IL-12, IL-13, and IL-15 are important cytokines that have not been studied previously in human autoimmune thyroid diseases. By applying RT-PCR on RNA extracted from tissue samples, we have investigated in vivo gene expression of these cytokines in multinodular goiter (MNG), Graves' disease (GD), and Hashimoto's thyroiditis (HT). In addition, in vitro studies were carried out using the transformed human thyroid cell line, HT-ori3, and primary thyroid cell cultures derived from patients with GD. These cells were used either unstimulated or stimulated for 12 h with TSH, IL-1, or interferon-gamma (IFN-gamma). IL-12 p40 gene expression was identified in 2 of 10 MNG samples, 6 of 12 GD, and 3 of 4 HT. HT-ori3 and primary thyroid cell cultures were positive for IL-12 p40 messenger RNA (mRNA) expression in both unstimulated and stimulated cell cultures. IL-13 mRNA was expressed in 2 MNG, 9 GD, and 1 HT sample. Both HT-ori3 and primary thyroid cultures expressed IL-13 after TSH, IL-1, or IFN-gamma stimulation; unstimulated primary cultures of thyroid cells, however, did not express IL-13. IL-15 gene expression was detected in 8 MNG, 8 GD, and 4 HT samples. HT-ori3 and primary thyroid cell cultures, stimulated with TSH, IL-1, or IFN-gamma, showed expression of this cytokine. Unstimulated cells showed only a weak expression. Our results indicate that the cytokine patterns in the various diseases studied are heterogeneous; that thyroid cells can express IL-12, IL-13, and IL-15 mRNA in culture, particularly after TSH, IL-1, or IFN-gamma stimulation; and that IL-15 is expressed in most of the tissue samples studied.

Autoimmune Diseases↗