CIRCADIAN-RHYTHM OF THE SOLUBLE P75 TUMOR-NECROSIS-FACTOR (STNF-R75) RECEPTOR IN HUMANS - A POSSIBLE EXPLANATION FOR THE CIRCADIAN KINETICSOF TNR-ALPHA EFFECTS

Circadian alterations of several immune functions in vivo are well est ablished, and may have important physiological and clinical implicatio ns, In line with this, tumor necrosis factor (TNF)-alpha has been impl icated in the circadian regulation of body temperature, As soluble TNF receptors (TNF-R) act as naturally occurring competitive inhibitors o f this cytokine, we investigated plasma levels of the soluble sTNF-R55 and sTNF-R75 in comparison with plasma cortisol and body temperature in nine healthy male volunteers during a defined 16 h light/8 h dark c ycle. It was found that sTNF-R75, but not sTNF-R55, exhibited a clear- cut circadian rhythm with a significant (P < 0,01) peak at 7:51 a,m. /- 58 min. The phase of the sTNF-R75 rhythm preceded that of cortisol by similar to 1 h and inversely corresponded to the circadian rhythm o f body temperature. Moreover, the individual amplitudes of sTNF-R75 an d body temperature exhibited a significant (P < 0,01) positive correla tion, These results suggest that (i) the two sTNF-R are regulated inde pendently, (ii) the sTNF-R75 rhythm is not primarily due to the cortis ol rhythm and (iii) the fluctuation of the sTNF-R may contribute to th e regulation of body temperature by modulating the availability of fre e TNF.