Transient stimulatory effects on pituitary-thyroid axis in patients treated with interleukin-2.

It has been shown that various cytokine therapies may influence thyroid hormone parameters that may lead to serious side effects including nonthyroidal illness. Interleukin-2 is effective in increasing CD4-T cell numbers in human immunodeficiency virus (HIV)-infected patients and it is used in the treatment of various malignant tumours. However, the association of interleukin-2 (IL-2) therapy and thyroid function is not clearly established as serial systematic measurements of thyroid parameters have not been performed with interleukin-2 as the sole therapeutic agent. Therefore, it was the aim of this study to examine prospectively the impact of a 5-day interleukin-2 therapy on thyroid parameters in asymptomatic HIV-infected patients. Twenty male euthyroid patients (mean age, 42.6 +/- 3.2 years; body weight, 73.4 +/- 3.0 kg) received 9,000,000 IU/d interleukin-2. Thyroid function was evaluated by measurements of serum thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4), free thyroxine (FT4), reverse T3 (rT3), thyroglobulin (Tg), thyroxine-binding globulin (TBG), and anti-thyroid-peroxidase (TPO)-antibodies from day 1-4 and on days 7, 14, 20, 40, 60, 80, and 100. All results are given as mean +/- SD. On day 4, we observed a significant increase that was still within normal range of T4 and T3 (p < 0.05). TSH increased from 1.33 +/- 0.57 to 4.53 +/- 1.39 mU/l (p = 0.0001) and FT4 from 18.1 +/- 4.2 to 48.9 +/- 10.9 pmol/L (p = 0.0001) on day 4 with a gradual decrease thereafter. Normalization to baseline levels for TSH (1.45 +/- 0.75 mU/L) and FT4 (18.1 +/- 3.0 pmol/L) was achieved only on day 14. The increase of FT4 was more pronounced (well in the hyperthyroid range) than the increase in total T4 in the presence of normal TBG and albumin concentrations whereas TBG was not affected. We did not observe changes in anti-TPO-antibody levels up to day 100. Our data clearly demonstrate that the administration of interleukin-2 has a stimulatory effect on the pituitary-thyroid axis. The increase of TSH suggests a central stimulation directed by the action of IL-2 as the major mechanism.

Comparison between subcutaneous and intravenous interleukin-2 treatment in HIV disease.

OBJECTIVES: Therapy of HIV-infection using intravenous interleukin-2 (IL-2) is known to be effective in terms of increasing CD4-counts but is associated with significant side-effects and hospitalization. However, the combination with protease-inhibitor therapy has not been tested yet. The aim of the present study was to investigate the safety and efficacy of intravenous vs. subcutaneous IL-2 regimes using 9 Mio I.U. of IL-2, in combination with protease-inhibitor therapy. DESIGN: All patients were treated with a combination of two reverse transcriptase inhibitors and a protease-inhibitor prior to IL-2 administration for at least 6 weeks. Ten patients were assigned to the intravenous IL-2 group (group A). 10 to the subcutaneous group (group B). RESULTS: In both treatment groups, CD4 count significantly increased shortly after the end of therapy (group A: 223% over baseline [day 7]; group B: 264% over baseline [day 7]). During the follow-up CD4 counts slowly decreased thereafter but remained above baseline 3 months following IL-2 treatment. The CD8 lymphocytes showed a similar but less pronounced pattern with a maximum at day 7 (group A: 116% over baseline, group B: 158% over baseline) and reached baseline earlier in the follow-up-period. Altogether the CD4/CD8-ratio was elevated through long periods on follow-up. Throughout follow-up, there were no apparent changes in viral load during IL-2 therapy in either groups. IL-2 therapy was administered for a mean time of 4.2+/-0.1 days in the intravenous group and of 4.8+/-0.1 days in the subcutaneous group until therapy was terminated at day 5 or due to side-effects. Only 1/10 patients completed the 5-day course of intravenous therapy in contrast to 6/10 in the subcutaneous group. CONCLUSIONS: Subcutaneous interleukin-2 using 9 Mio IU day(-1) in combination with protease-inhibitors showed equal efficacy as intravenous therapy and was associated with less side-effects.