Sir,
In a previous paper (Kauppila et a]. ,1982) we described the effects of human leukocyte interferon on serum sex steroid and peptide hormone concentrations during the menstrual cycle of normally cycling, healthy women. Serum estradiol and progesterone concentrations were significantly decreased during the treatment cycle, whereas no signijkant changes were observed in the serum peptide hormone concentrations, including LH and FSH. We interpreted these data as suggesting that interferon modulates the function of both L H and FSH by partially blocking their stimulatory action on ovarian steroidogenesis, possibly by interfering with the binding of LH and FSH to their respective cell-surface receptors. Because TSH also mediates its action through binding to membrane receptors, and because it has been suggested that a relationship exists between the structure and function of receptors for TSH and interferon in some in vitro models (see Friedman et al., 1982), we decided to extend our studies to evaluate the possible interaction of interferon administration with thyroid function in man in vivo.
The design of our experiment was described in the earlier report (Kauppila et al., 1982). Briefly, 3 x lo6 units of human leukocyte interferon, purified by Cantell et al. (1981), were administered by daily subcutaneous injection from the 3rd through the 24th day of the cycle in five volunteer women. Serum was stored at -20" C until assayed. T3, T4, free T4 and T3 uptake were determined in the same serum samples, as was TSH measured in the previous study (Kauppila et al., 1982). T3 and T4 were measured using Farmos radioimmunoassay reagents (Farmos Diagnostica, Turku, Finland), free T4 using Amerlex ree T4 RIA kits (Amersham International, Amersham, England) and T3 uptake using Nordiclab M A A T-3 TJT3 Uptake tests (Nordiclab, Oulu, Finland). Statistical significance was evaluated by employing paired t-tests on the individual values obtained from the control and treatment cycles (Fig. 1
, inset).
Only very minor fluctuations were seen in thyroid hormone concentrations during the control and treatment cycles. Daily administration of interferon induced significant decreases in the circulating concentrations of T3, T4 and free T4, whereas serum TSH was not significantly affected, Interferon treatment had essentially no effects on T3 uptake, indicating that the decreased serum levels of thyroid hormones were not due to alterations in their binding to thyroxine-binding globulin (TBG).
Assuming that interferon does not affect the metabolic clearance rate of thyroid hormones, these results support the idea that interferon elicits its action on thyroid hormone production at the thyroid cell membrane level. The effect observed, no change in the trophic hormone concentration, associated with decreased concentrations of the target tissue secretion products, is identical to that observed previously for FSH vs estradiol and LH vs progesterone (Kauppila et al., 1982). Taken together with in vitro data demonstrating interactions of interferon and TSH at the thyroid cell membrane level (see Friedman et al., 1982), our data suggest that the in vivo effects observed in this and in our previous study are due to membrane interactions rather than possible effects on the enzyme reactions involved in thyroid hormone synthesis or steroidogenesis. It is still not clear, however, whether the interaction between interferon and TSH is due to competition for a common binding site or to some other alteration in membrane function induced by interferon, which then would lead to decreased binding of TSH.
In agreement with our previous results (Kauppila et al., 1982), we suggest that therapeutic treatment with interferon, in addition to having antiviral, antiproliferative and immunomodulating activities, may also be effective via endocrine mechanisms. These may be important in the treatment of hormone-dependent neoplasms such as breast carcinoma (Sikora, 1980).