Production of interleukin (IL)-5 and IL-10 accompanies T helper cell type 1 (Th1) cytokine responses to a major thyroid self-antigen, thyroglobulin, in health and autoimmune thyroid disease.
Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma exert detrimental effects in organ-specific autoimmune disease, while both destructive and protective roles have been demonstrated for interleukin (IL)-10, IL-4 and IL-5. We examined the production of these cytokines by peripheral blood mononuclear cells (PBMC) from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD) and healthy controls, upon exposure to a thyroid self-antigen, human thyroglobulin (Tg), in the presence of autologous serum. Initially, TNF-alpha and IL-2 were produced in all three groups, accompanied by IL-10. Release of IFN-gamma, IL-4 and, notably, IL-5 ensued. Both patient groups exhibited increased TNF-alpha, IL-2, IFN-gamma and IL-10 responses, and PBMC from HT patients secreted lower amounts of IL-5 than male, but not female, controls. Enhanced TNF-alpha production by HT cells also occurred in the presence of pooled normal sera, indicating a dependency on intrinsic cellular factors. Conversely, higher production of TNF-alpha and IL-5 occurred in the presence of autologous sera than in the presence of pooled normal sera in both patient groups, indicating a dependency on serum constituents. Complement appeared to promote the production of IL-2 and particularly IL-5, the levels of which were reduced by neutralization of complement by heat- or zymosan treatment. The production of IFN-gamma and IL-2 of the three groups together correlated directly with the serum anti-Tg activity. Moreover, TNF-alpha, IFN-gamma, IL-5 and IL-10 responses were markedly inhibited by partial denaturation of Tg by boiling. We hypothesize that autoantibodies and complement may promote mixed Th1/Th2 cell cytokine responses by enhancing the uptake of autoantigens by antigen-presenting cells.
Nielsen
C H
CH
Institute for Inflammation Research, Copenhagen University Hospital, Copenhagen, Denmark. C.H.Nielsen@rh.dk
Hegedüs
L
L
Rieneck
K
K
Moeller
A C
AC
Leslie
R G Q
RG
Bendtzen
K
K
D000328:Adult; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006111:Graves Disease / Q000276:immunology*; D050031:Hashimoto Disease / Q000276:immunology*; D006358:Hot Temperature; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D011489:Protein Denaturation; D012737:Sex Factors; D013745:Tetanus Toxoid / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology*
D001324:Autoantigens; D016207:Cytokines; D015848:Interleukin-5; D013745:Tetanus Toxoid; D016753:Interleukin-10; D003165:Complement System Proteins; D013954:Thyroglobulin