CYTOKINES AND ENDOCRINE SYSTEM - IS IT ME ANINGFUL TO MONITOR MORE THAN THE THYROID-GLAND

Aim: It was the aim of this study to evaluate the occurrence, the degr ee, and clinical relevance of immunological phenomena in endocrine and non-endocrine organs as seen under therapy with interferon-alpha (IFN -alpha) and/or interleukin-2 (IL-2). Patients and methods: In 61 patie nts (age: 50.2 +/- 12.8 years) receiving cytokines as treatment for he patological cal or hemato-oncological diseases, parameters of the thyr oid gland, the gonadal system, the adrenal gland the pituitary gland, parameters of water and electrolyte-balance, and of bone metabolism we re measured. AU patients were treated with interferon in a mean dosage of 15.3 +/- 10.5 mio U subcutaneously per week. Additionally, 15 pati ents were treated with interleukin-2 (36.5 +/- 22.3 mio U subcutaneous ly per week). Among other assays, patients <<sera were screened for th e existance of autoantibodies against 30 different antigenic substrate s using an indirect immunofluorescence technique (IIF). Results: Pts, treated with IFN-alpha and IL-2 (n = 13) showed a significant inductio n of thyroid antibodies against thyroglobulin (anti-TG): 61 +/- 82 U/m l vs. 1000 +/- 2352 U/ml (p < 0.05) and against thyroid-peroxidase (an ti-TPO): 162 +/- 538 vs. 468 +/- 1071 U/ml (p < 0.05). In pts, only tr eated with IFN-alpha (n = 26), the increase of anti-TG from 69 +/- 97 to 134 +/- 178 U/ml and of anti-TPO from 20 +/- 21 to 21 +/- 19 U/ml w as insignificant. Patients with a combined treatment of IFN-alpha and IL-2 were mainly affected: 2 patients developed hypo- and 5 hyperthyro idism. Thus, regular controls of thyroid function during the entire du ration of therapy is justified. We were unable to show any influence o f the duration of treatment or dosage of cytokines on the endocrine an d non-endocrine parameters investigated. - In addition, 8 different AA B (against smooth/striated muscles, parietal cells, nuclear parts, mye lin, keratin, endothel, and neuroendothel) were detected by IIF which did not change under therapy. Two patients newly developed AAB during therapy, however none of them suffered from clinical symptoms. AAB aga inst endocrine organs other than the thyroid gland were not detected. No other endocrine system showed alterations of its function. Conclusi on: Based on the data of this study we conclude that the thyroid gland should he regularly monitored for immunological and functional change s during cytokine therapy. The results do not support a general recomm endation for a routine screening of other, non-thyroidal endocrine sys tems for autoimmune phenomena and alterations of function in each pati ent.