IL-10 expression in thyroid glands: protective or harmful role against thyroid autoimmunity?
IL-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 microg 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 gamma-32P-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-gamma)/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.
Department of Immunology, St Bartholomew's and the Royal London School of Medicine and Dentistry, UK.
J R
JR
de la Vega
J C
JC
Vilaplana
A
A
Biro
L
L
Hammond
G F
GF
Bottazzo
R
R
Mirakian
D000328:Adult; D002478:Cells, Cultured; D005260:Female; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D016753:Interleukin-10 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000209:etiology* / Q000276:immunology / Q000473:pathology
D006680:HLA Antigens; D016753:Interleukin-10