SUMMARYIL-10 is a cytokine which not only suppresses cellular immunity but also stimulates the humoral response. In certain animal models of autoimmunity, IL-10 exerts a protective effect against autodestruction. This study was to ascertain whether there could be a role for IL-10 in human autoimmune thyroid disease. Total RNA was extracted from snap-frozen thyroid blocks from surgical specimens. Five 'normal', five multinodular, six Graves and two Hashimoto thyroids (one euthyroid and one hypothyroid) were studied. Approximately 7 mg of total RNA from each gland were reverse transcribed with oligo-dT primers. Pre-plateau semiquantitative polymerase chain reaction (PCR) was performed with specific IL-10 primers. PCR products were run on a 1·5% agarose gel, blotted onto a N-hybond nylon membrane, hybridized with a specific internal probe labelled with g-32 P-ATP and autoradiographed. Statistical analysis of densitometric values showed significantly higher IL-10 levels in the autoimmune than in the non-autoimmune glands. In situ hybridization and immunohistochemistry showed that the IL-10 message was located within the infiltrating lymphomononuclear cells. Histological analysis revealed that the autoimmune thyroids with the highest IL-10 levels were characterized by relevant degrees of B and T cell infiltration and also exhibited the greatest percentage of spontaneous HLA class II expression on thyrocytes. IL-10 and neutralizing anti-IL-10 antibodies were not able to regulate in vitro spontaneous or interferon-gamma (IFN-g)/phytohaemagglutinin (PHA)-induced HLA class II on thyrocytes. We conclude that in active autoimmune thyroiditis, in addition to the well documented production of Th1 cytokines, Th2-related lymphokines can be detected simultaneously. It can be envisaged that in this condition the role of IL-10 might be directed to the stimulation of B cell proliferation and antibody production rather than to the suppression of proinflammatory cytokine release.
Ab initio SCF calculations using an extended basis set were performed in order to determine the tunneling frequency of the interconversion between the two asymmetric forms of P-hydroxyacrolein. Along the reaction coordinate, a double minimum profile with a barrier of 11.6 kcal/mol is found. Due to the value of the effective mass involved in the exchange along the reaction coordinate, the tunneling frequency that results is one order of magnitude less than the experimental value. The double minimum profile obtained when all the atoms but the intervening hydrogen are kept in the average position gives a tunneling frequency which is of the same order as the experimental value. This proton exchange mechanism also explains the change in tunneling frequency when an isotopic species is used.
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