CIRCADIAN ABNORMALITIES OF NATURAL-KILLER (NK) CELL-ACTIVITY AND IMMUNOREACTIVE ACTH IN THE PERIPHERAL-BLOOD OF PATIENTS WITH AUTOIMMUNE RHEUMATIC DISEASES

The hypothalamic-pituitary-adrenal (HPA) activity is admittedly import ant for synchronizing several variables of the circadian system. Natur al Killer (NK) cells are large granular lymphocytes spontaneously cyto toxic. They are involved in the immunosurveillance against viruses and cancer, whereas their role in autoimmunity is unclear. Both lymphokin es and hormones modulate NK cytotoxicity. In previous works we demonst rated that in healthy subjects NK activity of peripheral blood mononuc lear cells (PBMC) and in vitro susceptibility to physiological modifie rs have a temporal organization with a statistically validated circadi an rhythm. In rheumatoid arthritis (RA) and in other autoimmune diseas es abnormalities of both HPA function and NK cell activity have been r eported. We investigated the circadian profiles of serum ACTH, beta-en dorphin and cortisol on the one hand, and of NK cell cytotoxicity on t he other, in 7 hospitalized subjects affected by autoimmune diseases. Changes of NK cell activity after exposure in vitro to positive and ne gative modifiers were also evaluated. Blood was drawn at 4 hour interv als for 24 hours, starting at 08:00. NK activity was assessed with a d irect nonradiometric 4-hour cytolytic assay, using K562 cells as a tar get. Radioimmunoassayable ACTH, beta-endorphin and cortisol were measu red using commercially available kits. Circadian variations were stati stically validated with the Cosinor method. Normally synchronized, cir cadian rhythms were detected for serum beta-endorphin and cortisol, wh ereas significance was not attained for serum ACTH. Circadian variatio ns of spontaneous NK cell activity were apparent only in RA patients; mean acrophase was remarkably phase-shifted with respect to healthy co ntrols. We noticed individual rhythmicities also of percent changes af ter exposure to modifiers, yet no consistent pattern could be validate d. Our data suggest that in autoimmune rheumatic diseases the circadia n patterns of natural cytotoxicity and susceptibility to modifiers are lost in the majority, but not in all patients. Among HPA hormones, ci rcadian abnormalities are apparently much more frequent for immunoreac tive ACTH, than for beta-endorphin and cortisol.