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The possibility to detect initial "preclinical" pulmonary lesions related to asbestos is under debate. The aim of this study is to report our experience. We have submitted to HRCT 70 shipyard workers with chest X-ray judged "normal" by "outside" readers (mean age 44.5 +/- 6.1 ys) with a similar grade of (low-level) exposure to amosite (mean duration of "direct"/"heavy" exposure was 4.2 +/- 4.9 ys; "environmental"/"light" exposure was 8.4 +/- 5.9 ys). Among the 70 workers, in 34 pleural plaques were shown, in 6 subjects parenchymal abnormalities alone and in 13 parenchymal and pleural abnormalities were found; in the last 17 workers no pathological finding was shown. In six subjects the presence of a combination of parenchymal abnormalities permitted us to diagnose asbestosis. The difference in the duration of exposure to asbestos for the subjects with both pleural and parenchymal involvement compared to all other groups of workers was statistically significant; also the difference in duration of exposure between workers with or without parenchymal involvement resulted significant. In a control group (20 subjects without any known professional exposure to asbestos) HRCT permitted us to identify 5 cases with small pleural plaques while only one case presented parenchymal bands; lesion frequency was significantly lower in comparison with the exposed group. Calcified plaques have been proved to be more common in the workers with heavier exposure, and no one of the reference group had calcified plaques. The CT-determined emphysema score was found to optimally correlate with smoking habit (pack/years). In conclusion our study suggests that pulmonary or pleural involvement can be shown by HRCT before the onset of any clinical symptomatology with high sensitivity and specificity. Furthermore the results seem to indicate that the prevalence of HRCT-shown parenchymal lesions and the severity of lung involvement among asbestos-exposed workers are related to the duration of exposure, as in most of clinically evident asbestos-related lung disorders, in contrast with previous observations.

We have reexamined a series of 1119 patients consecutively submitted to fine needle aspiration of nodules of the neck. Among these in 166 cases ultrasonography combined with aspiration suggested the presence of cysts. 60 patients were submitted to cyst aspiration and 34 were aspirated and submitted to cyst injection with tetracycline hydrochloride. The patients were followed up clinically and ultrasonically 3 and 12 months after treatment. Cure was defined as the absence of any residual cystic lesion and an ultrasonic cyst volume less than 50% with respect to basal after 12 months from the start of treatment. 18 of the 60 (30%) patients only aspirated and 24 of the 34 patients (70%) in the tetracycline group were cured (statistically significant; p < 0.005). We conclude that tetracycline seems an effective sclerotherapy in treatment of thyroid cysts.

Thyroid adenoma is commonly associated with surgery and radiometabolic treatment; recently, according to previous successful reports, percutaneous ethanol injection therapy under sonographic guidance, has been introduced as an alternative. This technique has already been favourably used in the treatment of focal lesions, such as liver cancer and hyperparathyroidism. In our experience, we have treated with such therapy 69 patients affected by thyroid adenoma (55 females, 14 males; 28 pretoxic, 41 toxic). Ethanol (0.5-2.8 mL/mL nodular tissue) was injected, under sonographic guidance, in 4-9 sessions (1 weekly). Thyroid hormone profile was assessed during treatment and at 3 and 6 months follow-up. Apart from local transient pain in 21% sessions, two cases of pyrexia (38.5 degrees-1 day) and 3 cases of transient dysphonia, no relevant adverse effects were observed. A slight thyroid hormone increase was seen in both groups immediately following treatment. Six months after therapy a biochemical and clinical remission of hyperthyroidism was observed in 33 out of 41 toxic patients (80%); a significant increase of TSH levels was seen in both groups (p < 0.001). With follow-up, significant volume shrinkage (70-80% volume reduction--p < 0.0001) as well as structural alterations of the nodule, were consistently recorded at sonography, in both groups; a linear relationship (p < 0.0001) between pretreatment volume and volume reduction was found. At scintiscan functional activity of extranodular parenchyma was found in 75% of patients affected by pretoxic adenoma and in 63.1% of patients with toxic adenoma. These data confirm that percutaneous ethanol injection therapy is effective in obtaining functional ablation and in inducing remission of hyperthyroidism, when present; so it represents a valid and safe alternative to standard therapeutic tools of thyroid adenoma.

Three patients affected with Graves' ophthalmopathy and pretibial myxoedema have been treated with high dose intravenous immunoglobulins. We have observed in all patients clinical improvement of pretibial myxoedema and a parallel reduction or negativization of the titre of circulating thyroglobulin, microsomal, TSH receptor autoantibodies and of non organ-specific antibodies (antinuclear, anti smooth muscle cells and antimitochondrial autoantibodies). In conclusion the results of this study suggest that intravenous immunoglobulin are effective in the treatment of pretibial myxoedema and probably act by an immunomodulation of autoimmune phenomena.

We report the effect of "intravenous gamma-globulin treatment" (IVIG) in a patient with autoimmune polyglandular syndrome type II, with circulating organ specific autoantibodies, preclinical hypothyroidism, amenorrhea and Addison syndrome. During IVIG treatment we observed a normalization of thyroid function, the appearance of some non ovulatory menses, reduction of thyroglobulin, thyroidal microsomal, anti-parietal cell, adrenal and ovary antibodies. These data confirm that intravenous immunoglobulin may represent a new tool for treatment of autoimmune disorders and show, for the first time, an immunosuppressive effect of intravenous gammaglobulin treatment in immunological phenomena direct against ovary, adrenal and gastric mucosa.

The aim of this study was to evaluate the variations of thyroid autoantibodies titre in a group of 15 patients affected with "Graves' disease" (G. D.) during the treatment with antithyroid drug (ATD) and "high dose intravenous immunoglobulin" (IVIG) for "Graves' ophthalmopathy". Before the starting of treatment thyroglobulin antibodies (TgAb) were positive in 10/15 patients, microsomal antibodies (MAb) were positive in 13/15 patients and TRAb were positive in 5/9 patients. At the end of treatment TgAb titre was decreased or negative in 7/10 patients, MAb titre was decreased or negative in 7/13 patients, TRAb titre was diminished or negativized in 5/5 patients. Anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) were positive in 3/15 and 3/15 patients before the treatment and in all these we observed a reduction or negativization of circulating titre during IVIG treatment. Anti-extractable nuclear antigen (ENA)m anti-mitochondrial antibodies (AMA) and rheumatoid factors were negative in all the patients. Also in the 3 patients not treated with ATD we have observed a reduction or a negativization of circulating thyroid autoantibodies. In conclusion these data suggest that the reduction of thyroid and non organ specific autoantibodies might be due to a stable immunosuppressive action of IVIG treatment in patients with Graves' disease.

Recent reports of transmission by intravenous gamma-globulin preparations of A, B, C and non-A non-B hepatitis (NANBH), including several cases that progressed to severe liver damage and death, have raised concerns about the safety of intravenous gamma-globulins. To assess this issue 15 patients treated with high-dose "intravenous immunoglobulin" (IVIG) for Graves' Ophthalmopathy had serial determination of glutamic pyruvic transaminase (GPT), glutamic oxalacetic transaminase (GOT), gamma glutamyltranspeptidase (gamma-GT), alkaline phosphatase and bilirubin that were performed regularly at interval of 3 weeks during IVIG treatment and 6 months after the end of the treatment. Hepatitis A, B, C and HIV markers were determined before, during and 6 months after the end of the treatment. The standard dosage was 400 mg per Kg body weight IVIG (3 cycles of 5 days and 12 of 1 day, every 21 days). Transient minor elevations were observed for GPT, for GOT, for gamma-GT and alkaline phosphatase. None of the elevations were considered indicative of NANBH or of any chronic hepatic disease. Transient presence of hepatitis A, B and C antibodies were observed in 6 patients. All patients remained negative for hepatitis B antigens throughout the study. HIV antibodies resulted always negative in all patients. In conclusion this study suggests the hepatitis and HIV safety of IVIG.

We have evaluated the variations of thyroid function, of thyroid autoantibodies titer, of non-organ specific autoantibodies and of other autoimmunity indices in 3 patients affected with Hashimoto's thyroiditis treated with "high dose intravenous gammaglobulin" (IVIG) (400 mg/Kg/day for 3 cycles of 5 days and subsequently 9-12 cycles of 1 day every 21 days). Before the starting of IVIG treatment patient 1 presented clinically evident hypothyroidism while patients 2 and 3 presented a preclinical form of hypothyroidism. At the end of IVIG treatment patients presented no variation of thyroid function, while patients 2 and 3 presented a normalization of T3, T4 and TSH circulating levels. Before the starting of IVIG treatment thyroglobulin antibodies (TgAb) were positive in 3/3 patients, microsomal antibodies (MAb) were positive in 3/3 patients adt TRAb were positive in 2/3 patients and MAb titre was decreased or negative in 0/3 patients. At the end of IVIG treatment Tg Ab titre was decreased or negative in 2/3 patients and MAb titre was decreased or negative in 2/3 patients. Anti-nuclear antibodies (ANA) 1/3 patients before the titre and in all these we observed a reduction or negativization of circulating titre during IVIG treatment. Anti-extractable nuclear antigen (ENA), anti-mitochondrial antibodies (AMA), C3, C4, CH50 and rheumatoid factors were negative or in the normal range in all the patients. In conclusion these data suggest that IVIG is effective in the treatment of preclinical hypothyroidism in patients with Hashimoto's thyroiditis and determine a stable immunosuppressive action on circulating thyroid and non organ specific autoantibodies.

The most frequently used medical treatment of Graves' ophthalmopathy is the combination of orbital irradiation and systemic corticosteroid. In this study the effectiveness of "high dose intravenous immunoglobulin" (IVIG) in Graves' ophthalmopathy treatment is explored. 11 patients were treated with orbital radiotherapy combined with systemic corticosteroid (Group 1), while 10 patients were treated with the combination of orbital irradiation and IVIG (Group 2). The therapeutic effect was assessed by an ophthalmopathy index based on the American Thyroid Association, classification of ocular changes of Graves' ophthalmopathy. All signs and symptoms of endocrine ophthalmopathy improved significantly in both groups. The mean ophthalmopathy index decreased from 7.0 +/- 1.3 to 3.4 +/- 1.5 in Group 1, and from 7.0 +/- 1.8 to 3.0 +/- 2.1 in Group 2. Statistical analysis showed no significant difference between Group 1 and 2 mean initial and final ophthalmopathy index, and a significant difference between initial and final ophthalmopathy index both in Group 1 and 2. While side effects were present in Group 1 treated with systemic corticosteroid, no side effect was observed in patients treated with IVIG. These preliminary results suggest that IVIG is safe and effective in the treatment of Graves' ophthalmopathy.

In the ductal epithelium adjacent to lymphoid infiltrates and in lymphocytes of salivary glands in patients with Sjögren syndrome (SS), there is an increased expression of monokine induced by interferon (IFN)-γ(MIG) and chemokine (C-X-C motif) receptor 3 (CXCR)3, which therefore seems to participate in the SS pathogenesis. Cultured SS salivary epithelial cells treated with IFN-γ release high levels of IFN-γ-inducible protein 10 (IP-10) and MIG. MIG secreted by salivary epithelial cells (under IFN-γ influence), recruits Type-1 helper (Th1) lymphocytes that create an amplification feedback loop, and perpetuates the autoimmune process, through an enhanced IFN-γ induction, that in turn stimulates an additional MIG secretion from epithelial cells. The high levels of MIG in saliva and tears indicate an immune Th1 dependent response. An amelioration of autoimmune sialadenitis with MIG antagonists has been observed in experimental settings, suggesting a possible therapeutic approach to SS. More investigations are needed to assess whether MIG is a novel therapeutic target for SS in humans. [ABSTRACT FROM AUTHOR]

Monokine induced by interferon (IFN)-γ (MIG) and its receptor chemokine (C-X-C motif) receptor 3 (CXCR)3 seem to play an important role in the pathogenesis of rheumatoid arthritis (RA). MIG expression has been observed in sera, synovial fluid (SF) and synovial tissue of RA patients; it is highly expressed in RA synovium by infiltrating macrophage-like cells and fibroblast-like synoviocytes. A Type-1 helper-response orientated disease was suggested because of the high expression of CXCR3 in SF T cells and the presence of elevated IFN-γ levels. It has been observed a decrease of the inflammation by anti-CXCR3, and anti-MIG molecules, in fact they inhibit CXCR3- enhanced cell migration and pro-inflammatory cytokine expression, leading to an amelioration of the arthritis progression. These findings suggest a possible therapeutic role of these molecules in humans. [ABSTRACT FROM AUTHOR]

In Type 1 Diabetes (T1D), the monokine induced by interferon (IFN)-γ (MIG)/(C-X-C motif) receptor (CXCR)3 axis has a crucial role in β-cell destruction and in the autoimmune process of the disease, like many papers have reported. In fact, in T1D subjects the serum levels of the Type helper 1 chemokine MIG is increased, suggesting that this chemokine could be a predictive marker of T1D. Moreover, the pathophysiology of the disease course could be assessed by measuring MIG serum levels. A potential approach for T1D therapy could be the block of MIG expression at the beginning of the disease. Anyway, the chemokines-cytokines interactions in the T1D pathogenesis need to be further investigated. [ABSTRACT FROM AUTHOR]

Chemokine (C-X-C motif) ligand (CXCL)9/monokine induced by interferon (IFN)-γ (MIG) and its receptor, chemokine (C-X-C motif) receptor (CXCR)3, are involved in the pathogenesis of Graves' ophthalmopathy (GO). In tissues, recruited Type 1 helper (Th1) lymphocytes could cause an increased production of IFN-γ and tumor necrosis factor (TNF)-α, which in turn stimulate MIG secretion from these cells; all this creates an amplification feedback loop, and perpetuates the autoimmune process. In particular, MIG is secreted by fibroblasts and preadipocytes under the influence of IFN-γ. The IFN-γ induced MIG secretion in vitro, in GO fibroblasts and preadipocytes can be modulate by peroxisome proliferator-activated receptors (PPAR)-γ and PPAR-α activators. High levels of MIG in peripheral liquids could be considered as a marker of an especially Th1 orientated immune response. The presence of circulating MIG is associated with the active phase of GO. An increased concentrations of MIG in patients with GO reflect, at least in part, the orbital inflammation activity. Since MIG concentrations are significantly reduced during corticosteroids and/or radiotherapy treatments, with respect to control group and basal values of patients with GO, MIG has been proposed as a marker in the therapy choice for patients with GO. More studies are needed to investigate interactions between chemokines and cytokines in the GO pathogenesis and to evaluate whether MIG is a novel therapeutic target in these autoimmune disorders. [ABSTRACT FROM AUTHOR]

The monokine induced by interferon (IFN)-γ (MIG) and its receptor, the chemokine (C-X-C motif) receptor (CXCR)3, appear to contribute to the pathogenesis of autoimmune thyroiditis (AT). MIG is secreted by thyrocytes under the influence of IFN-γ. In tissue, recruited Th1 lymphocytes may be responsible for enhanced IFN-γ, which in turn stimulates MIG secretion from thyrocytes creating an amplification feedback loop, and perpetuating the autoimmune process. Circulating MIG and IFN-inducible T-cell α chemoattractant (I-TAC) levels are increased in patients with thyroiditis and hypothyroidism and are related to each other. The importance of a Th1 immune attack in the initiation of AT has been demonstrated. MIG levels were significantly higher in elder patients, or in those with a hypoechoic ultrasonographic pattern, or with hypothyroidism. In peripheral fluids, high MIG levels are considered a marker of host immune response, in particular Th1 orientated T-cells. Other studies are needed to continue to investigate the role of MIG as a novel therapeutic target in AT. [ABSTRACT FROM AUTHOR]

Type-1 helper (Th1) dependent chemokines, such as monokine induced by interferon (IFN)-γ (MIG) seem to contribute to the Graves' disease (GD) pathogenesis. The thyrocytes secrete the chemokine (C-X-C motif) ligand (CXCL)10 under the IFN-γ influence. Therefore, high levels of MIG in peripheral liquids indicate a Th1 orientated immune response and are associated with the active phase of GD in hyperthyroid patients (newly diagnosed and relapsing). Methimazole (MMI), used for the hyperthyroidism treatment, causes a reduction of the MIG secretion by isolated thyrocytes, a decrease of serum MIG levels and leads to a shift from a Th1 to Th2 response in patients with GD in the active phase. The Th1 lymphocytes recruited in the tissues enhance the IFN-γ and tumor necrosis factor (TNF)-α production, that in turn stimulate MIG secretion from these cells; this mechanism originates an amplification feedback loop, causing a perpetuation of the autoimmune process. It has been seen that peroxisome proliferator-activated receptors (PPAR)-γ and PPAR-α activators can modulate the IFN-γ induced MIG secretion in vitro, in GD thyrocytes. More studies are needed to examine the interactions between cytokines and chemokines in the GD pathogenesis and to evaluate the role of MIG as a new therapeutic target. [ABSTRACT FROM AUTHOR]

Different studies investigated about the role of T-helper 1 cytokines and chemokines in primary biliary cirrhosis (PBC). Animal models with autoimmune cholangitis have been used to investigate the involvement of (C-X-C motif) receptor (CXCR)3 and its ligand (C-X-C motif) ligand (CXCL)9/monokine induced by interferon (IFN)-γ (MIG) in the pathogenesis of PBC, suggesting a contribution of MIG in the development of PBC. In patients with PBC, in particular at the level of the portal areas of diseased livers, MIG expression and CXCR3+ cells have been found. MIG is positively associated with the severity of liver fibrosis. In PBC, circulating MIG levels and CXCR3+ cells are related with the progression of the disease; in fact, their expression increases significantly in PBC patients with respect to controls. Furthermore, it has been shown a significant reduction of these chemokines in the serum of PBC patients after treatment with ursodeoxycholic acid. [ABSTRACT FROM AUTHOR]

High levels of chemokine (C-X-C motif) receptor (CXCR)3 and monokine induced by interferon (IFN)-γ (MIG) expression were revealed in the intestinal mucosa of mice with experimental colitis, and in lymphocytes, macrophages and epithelial cells of patients with Crohn's disease (CD). CXCR3 and its chemokines expression were induced by IFN-γ in epithelial intestinal cells. These chemokines are involved in the recruitment of granulocytes and mononuclear cells, therefore in the maintenance of inflammation in CD. Serum MIG levels reflect CD disease activity, and it could be a marker for the responsiveness of patients to treatments. Efforts have been made to block MIG or CXCR3 in CD as a potential therapy of CD. [ABSTRACT FROM AUTHOR]

Several studies demonstrated the presence of an elevated expression of chemokine (C-X-C motif) ligand (CXCL)9/monokine induced by interferon (IFN)-γ (MIG) on macrophages and in T cells in perimysial infiltrates of patients with dermatomyositis (DM), and of chemokine (C-X-C motif) receptor (CXCR)3 expression on the majority of T cells in the same patients. This underlines the importance of T helper 1-mediated immunity, and in particular the MIG/CXCR3 interaction, in the immunopathogenesis of DM. The importance of MIG has been confirmed by a study on patients with DM about the presence of chemokines and their receptors in infiltrating cells at the level of lesional skin. This study showed that type I IFN chemokines, in particular MIG, are firmly related with the active disease and its clinical score in juvenile DM, suggesting the importance of chemokines trend in monitoring disease activity and in the treatment indication. [ABSTRACT FROM AUTHOR]

The chemokine monokine induced by interferon (IFN)-γ (MIG) is expressed in idiopathic inflammatory myopathies muscle. Abundant expression of MIG was observed on macrophages and T cells surrounding and invading non-necrotic muscle fibers in polymyositis and in inclusion-body myositis and in T cells in perimysial infiltrates of dermatomyositis. MIG is also localized to blood vessel endothelial cells in all inflammatory and normal muscle tissues and it exerts its biological effects mainly via binding to the chemokine (C-X-C motif) receptor (CXCR)3. Serum MIG is high in patients with inflammatory myopathies. Human skeletal muscle cells might actively self-promote muscular inflammation by eliciting MIG secretion, under the influence of cytokines (IFN-γ, tumor necrosis factor-α), which can amplify Th1 cell tissue infiltration in vivo. It has been shown that drugs able to block the MIG/CXCR3 axis can suppress inflammation in muscle. [ABSTRACT FROM AUTHOR]

Many studies reported that monokine induced by interferon (IFN)- γ(MIG), and its receptor chemokine (C-X-C motif) receptor (CXCR)3, are expressed by T cells in different types of cutaneous damages associated with lupus, and that the CXCR3-activating chemokines are produced locally, suggesting that they play a significant role in the recruitment of T cells in these inflammatory lesions. Circulating MIG levels are increased in cutaneous Systemic Lupus Erythematosus (SLE) patients and strongly correlated with the disease activity. The data discussed in this review show that there is an increasing evidence that MIG may participate in the pathogenesis of a variety of the manifestations of cutaneous SLE, even if the exact role of MIG in the pathogenesis of this disease remains to be clarified. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a systemic inflammatory disease, affecting any organ, and that can be discovered by accident in approximately 5% of cases. High levels of the type-1 helper (Th1)-dependent chemokine, monokine induced by interferon (IFN)-γ (MIG)/chemokine (C-X-C motif) ligand (CXCL)9, and its receptor CXCR3 have been reported in bronchoalveolar lavage and biopsy samples of patients with sarcoidosis. These elevated levels are related with the amount of CD4+ lymphocytes and total lymphocytes. Alveolar macrophages resulted stained positive for all CXCR3 ligands and produced elevated levels of these chemokines. It has been shown that the epithelioid and giant cells of the sarcoid lungs were stained positive for MIG, IFN-inducible T-cell a chemoattractant (I-TAC) and IFN-γ-inducible protein 10 (IP-10), suggesting that MIG plays an important role in the accumulation of Th1 lymphocytes in sarcoid lungs. In addition, serum levels of MIG were related with the severity of the disease, and a correlation between the serial measurements of MIG and the clinical course of the disease was shown, indicating MIG as a potentially useful biomarker of sarcoidosis and its severity. [ABSTRACT FROM AUTHOR]

Several studies have proposed in Systemic sclerosis (SSc) patients that the monokine induced by interferon (IFN)-γ(MIG)/chemokine receptor (CXCR)3 axis has a determinant role in the autoimmune process and in fibrosis. Elevated MIG levels were linked to a more severe clinical phenotype, with kidney, lung and thyroid involvement. Then MIG could be considered a marker of a more aggressive autoimmune process. In vitro, SSc fibroblasts have different kinds of dysregulation in the secretion of MIG, once treated with cytokines (as interferons). Moreover, MIG has been suggested as a serologic marker of a more severe SSc form, so it could be useful for the risk stratification of SSc patients. [ABSTRACT FROM AUTHOR]