LACK OF INTRATHYROIDAL TUMOR-NECROSIS-FACTOR-ALPHA IN GRAVES-DISEASE

In vitro tumor necrosis factoralpha (TNFalpha) exerts a synergistic action on HLA class II expression and a cytotoxic action in FRTL-5 cells. Therefore, a role for TNFalpha as a local mediator of cell destruction in thyroid autoimmunity has been postulated. To elucidate the in vivo significance of these and other in vitro findings for the pathophysiology of Graves' disease we investigated 11 thyroid glands of patients suffering from Graves' disease for TNFalpha. In situ hybridization was done with a TNFalpha probe synthesized with T7 polymerase on a 750-base pair EcoRI fragment of the coding region. Primers at positions 152 and 854 in the TNFalpha copy DNA sequence were used for reverse polymerase chain reaction (PCR) amplification of TNFalpha in 5 patients. Immunohistological staining for TNFalpha was done with a mouse monoclonal antibody. We could not detect any TNFalpha and TNFalpha messenger RNA in thyroid tissue of 11 patients suffering mostly from relapsing Graves' disease by immunohistology and in situ hybridization as well as reverse PCR, respectively. A faint signal could be detected by reverse PCR in control thyroid tissue from a patient with recurrent goiter. This lack of intrathyroidal TNFalpha in relapsing Graves' disease is in accordance with a lack of increased TNFalpha production by T cell clones isolated from Graves' disease thyroid glands and contrasts with previous in vitro results. Since protective TNF actions have been demonstrated in other autoimmune diseases it could therefore be envisaged that the lack of intrathyroidal TNFalpha may be associated with the relapse of Graves' disease in our patients.