MODULATION OF CHRONIC EXCESSIVE INTERLEUKIN-6 PRODUCTION IN MULTIPLE-MYELOMA DOES NOT AFFECT THYROID-HORMONE CONCENTRATIONS

Interleukin-6 (IL6) is believed to be involved in alterations of thyro id hormone metabolism in acute nonthyroidal illness, To evaluate the e ffects of IL6 on thyroid hormone metabolism in a chronic IL6-mediated disease, we measured thyroid hormone concentrations in multiple myelom a patients treated with intravenous anti-IL6 chimeric monoclonal antib odies ([cMabs] K-d = 6.25 x 10(-12) mol/L). Twelve patients were studi ed, receiving at least one complete treatment cycle of 14 days (daily dose: 5 mg, n = 3; 10 mg, n = 3; 20 mg, n = 3; and 40 mg, n = 3). Eigh t of them also completed a second treatment cycle of 14 days. Thyroid hormone concentrations were measured before, during, and after treatme nt with the anti-IL6 cMab. Even in the group with the lowest dosage, I L6 activity measured by the B9 bioassay was blocked completely. Compar ed with the reference ranges, 10 of 12 patients had one or more abnorm al pretreatment values for thyroid hormone concentrations. Thyroid aut oantibodies were negative in all patients. There was no correlation be tween thyroid hormone concentrations and IL6 levels, although plasma I L6 levels were increased in all but one subject. Moreover, neutralizat ion of free IL6 by the anti-IL6 cMab did not affect thyroid hormone co ncentrations, although IL6-dependent C-reactive protein (CRP) levels d ecreased to undetectable levels in 11 of 12 patients, Two patients dev eloped infectious complications resulting in increased free IL6 and CR P levels and in profound alterations of thyroid hormone levels consist ent with an acute euthyroid sick syndrome. We conclude that IL6 is not a major determinant of thyroid hormone abnormalities in a chronic dis ease like multiple myeloma, but IL6 may be involved in thyroid hormone metabolism in acute diseases (probably in combination with other fact ors). Copyright (C) 1997 by W.B. Saunders Company.