RELATIONSHIP OF THE INCREASED SERUM INTERLEUKIN-6 CONCENTRATION TO CHANGES OF THYROID-FUNCTION IN NONTHYROIDAL ILLNESS

Variations in the serum concentration of interleukin-6 (IL-6) have bee n reported concomitantly with thyroid dysfunction: increased serum IL- 6 levels have been found in patients with thyroidal destructive proces ses, such as subacute thyroiditis, some forms of amiodarone-induced th yrotoxicosis, or after percutaneous ethanol injection into ''hot'' thy roid nodules, as a result of the cytokine release from the damaged thy rocyte. In addition, recent in vitro evidence suggests that IL-6 might account, at least in part, for changes of thyroid economy found in no nthyroidal illness (NTI). In this cross-sectional study we addressed t his problem by measuring serum IL-6 levels in 71 patients with NTI, du e to neoplasia (n=25), chronic liver disease (n=9), chronic renal fail ure (n=28), or other chronic nonthyroidal disorders (n=9). These patie nts had reduced mean serum total T3 (TT3) and free T3 (FT3) concentrat ions, normal total and free T4 levels, normal TSH values, and increase d serum reverse T3 (TT3) concentration (with the exception of chronic renal failure patients, who had normal rT3 levels). Serum IL-6 concent ration was increased above normal (i.e. >100 fmol/L) in almost all NTI patients, especially in those with low T3 values (median value: 258 f mol/L, range 73-3210, vs 152 fmol/L, range <12.5-460, in patients with normal TT3 values, p<0.001). Serum IL-6 values in NTI patients were n egatively correlated with serum FT3 values (r=0.56, p<0.001), and posi tively correlated with serum rT3 values (r=0.78, p<0.001). The increas ed serum IL-6 levels might represent a systemic reaction to disease, p ossibly mediated by stimulation of IL-6 synthesis and release induced by other cytokines, such as IL-l and tumor necrosis factor. Whether IL -6 is simply a marker of NTI or is responsible, at least in part, for abnormalities of thyroid function tests, as suggested by previous in v itro evidence, remains to be established.