To determine whether monocyte-derived humoral factors such as tumor necrosis factor-alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and IL-6 modulate serum thyroid hormone levels in infectious disorders, we measured serum levels of these monocyte-derived products, T3, T4, and C-reactive protein (CRP) in 59 out-patients with acute respiratory infection, aged 5 months to 15 yr (mean +/- SD, 5.7 +/- 4.2 yr). To minimize individual variation in their clinical and nutritional conditions, we selected out-patients with fever lasting for at least 3 days who had no severe disturbance of food intake. Serum T3 concentrations tended to be low in these subjects; 3 (5.1%) had levels below 1.2 nmol/L, L, and 13 (22.0%) had levels below 1.5 nmol/L. Serum T3 levels in 22 patients with elevated IL-6 (> 15 pg/mL) were significantly lower than those in 19 patients with normal IL-6 (< or = 5 pg/mL; T3, 1.7 +/- 0.4 vs. 2.2 +/- 0.6 nmol/L; P < 0.05). The serum IL-6 concentration was correlated inversely with the serum T3 level (r = -0.324; P = 0.012) as well as the T3/T4 ratio (r = -0.279; P = 0.032). Furthermore, a significant negative correlation was observed between CRP (induced mainly by IL-6) and T3 (r = -0.408; P = 0.001) or the T3/T4 ratio (r = 0.302; P = 0.020). On the other hand, TNF alpha was measurable in only 9 of 59 patients, and there was no correlation between TNF alpha and levels of thyroid hormone, CRP, or IL-6. Serum IL-1 beta was weakly detected in only 1 patient. On follow-up study of 10 of these patients, the serum T3 and T3/T4 ratio increased significantly with a reciprocal decrease in IL-6 and CRP during convalescence. No remarkable change in the serum T4 level was observed in our study. Our data suggest that the euthyroid sick syndrome is relatively common in children with acute respiratory infection, and IL-6 appears to mediate this syndrome in infectious disorders.