INFLUENCE OF CIRCADIAN-RHYTHM ON 41.8-DEGREES-C WHOLE-BODY HYPERTHERMIA INDUCTION OF HEMATOPOIETIC GROWTH-FACTORS

It has previously been reported by the authors that the induction of a series of cytokines by 41.8 degrees C Whole Body Hyperthermia (WBH), i.e., interleukin (IL)-1 beta, IL-6, IL-8, IL-10, tumour necrosis fact or cu, and granulocyte colony stimulating factor (G-CSF). As cytokine levels are known to fluctuate as a function of time, i.e. circadian rh ythm, the influence of circadian time structure on specific haemotopoe tic growth factors is studied, i.e. granulocyte macrophage colony stim ulating factor (GM-CSF), G-CSF and IL-3. Samples derived from four can cer patients undergoing extracorporeal WBH resulted in the following o bservations: G-CSF is induced by WBH, but unaffected by circadian rhyt hm, IL-3 fluctuates with circadian rhythm, but is unaffected by WBH. S pecifically, a biphasic temporal pattern of IL-3 (i.e. with a peak at 2:00 and 5:00 a.m. and a nadir concentration at 5:00 p.m.) was found b y analysis of variance. GM-CSF was below the lower detection limit pre and post WBH. The data show the importance of measuring cytokines as a function of time to circumvent conflicting results in the inter-rela tionship of 'true' cytokine induction and circadian rhythm. The implic ations of the differential induction of G-CSF, GM-CSF, and IL-3 for my eloprotection after WBH are discussed.