Circadian variations of interferon-induced enhancement of human natural killer (NK) cell activity.
We searched for circadian changes in the enhancement of the NK activity after exposure to IFN-gamma of peripheral blood mononuclear (PBM) cells obtained serially throughout the 24-h cycle. In August-October 1986, blood was drawn from 7 healthy, diurnally active and nocturnally resting male volunteers (22-34 yr) at 4-h intervals for 24 h starting at 08:00. PBM cells were immediately separated and assayed for NK cell activity, using K 562 cultured cells as a target in a 4-h 51Cr release assay after prior incubation for 20 h with buffer or 300 IU rIFN-gamma. Circadian variations of the spontaneous NK cell cytotoxicity were apparent; the activity was at its maximum at the end of the night or in the early morning and then declined in the afternoon. The 24-h rhythmic pattern was validated with statistical significance by the Cosinor method (p less than 0.02; acrophase 04:22). Maximum enhancement by IFN-gamma was attained in the second part of the night or in the early morning, i.e. in phase with the peak of the spontaneous NK cell activity. A significant circadian rhythm of the percent increase above control levels was validated by the Cosinor method (p less than 0.01; acrophase 04:03). Our findings may be of relevance to a better understanding of the mechanisms of control of human NK activity and warrant consideration as an approach to improve the effectiveness of time-qualified immunotherapy.
D000328:Adult; D002940:Circadian Rhythm; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology
D011994:Recombinant Proteins; D007371:Interferon-gamma