Antithyroid drugs and release of inflammatory mediators by complement-attacked thyroid cells.
Thyroid cells are exposed to complement attack in Graves' disease and Hashimoto's thyroiditis, but are resistant to killing by homologous complement. We have examined the effects of sublethal complement attack on thyroid cells in vitro. Extracellular reactive oxygen metabolites were produced and prostaglandin E2, interleukin-1 alpha, and interleukin-6 were released after complement attack. Cells pretreated with interferon-gamma and interleukin-1 alpha, which increase expression of CD59, were more resistant to these effects of complement. Conversely, blockade of CD59 with monoclonal antibody increased complement-mediated oxygen radical production and release of prostaglandin E2, interleukin-1 alpha, and interleukin-6. The antithyroid drugs methimazole and propylthiouracil abolished or reduced oxygen radical production by complement-attacked thyroid cells and reduced cytokine release. These results suggest that sublethal complement attack in autoimmune thyroid diseases exacerbates tissue injury by causing thyroid cells to release potent phlogistic mediators, although some degree of protection may be afforded in vivo by cytokine-mediated upregulation of CD59. Antithyroid drugs, concentrated within thyroid cells, will prevent the release of these inflammatory molecules, which may in turn explain the amelioration of thyroiditis and remission of Graves' disease after such treatment.
Weetman
A P
AP
Department of Medicine, University of Sheffield Clinical Sciences Centre, Northern General Hospital, UK.
Tandon
N
N
Morgan
B P
BP
D015703:Antigens, CD / Q000276:immunology*; D018957:CD59 Antigens; D003171:Complement Pathway, Classical / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D005609:Free Radicals; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology*; D008713:Methimazole / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D011441:Propylthiouracil / Q000494:pharmacology; D011458:Prostaglandins E / Q000378:metabolism*; D013961:Thyroid Gland / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D015703:Antigens, CD; D018957:CD59 Antigens; D005609:Free Radicals; D007375:Interleukin-1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011458:Prostaglandins E; D008713:Methimazole; D011441:Propylthiouracil; D007371:Interferon-gamma; D010100:Oxygen