Competition of IL-7 and IL-1ra determines lymphocyte response to delayed stimulation with PHA

Background: Human peripheral blood mononuclear cells (PBMC) left in microcu ltures for 24 h without mitogen do not respond to subsequent stimulation wi th PHA. They regain reactivity if the native culture medium is absorbed wit h other party lymphocytes or partially replaced with the medium from a PHA- stimulated culture. The observations suggest that, during the incubation, s ome inhibitory agent had accumulated in the culture medium. Aim: The study was performed to determine the nature of the observed phenom enon in respect of the possible role of monocytes and their products IL-1 a nd IL-1 receptor antagonist (IL-1ra), and to test for immunodiagnostic purp oses the significance of quantifying the lymphocyte response to delayed sti mulation with PHA in patients suffering from inflammatory processes. Methods: Lymphocyte response to delayed stimulation with PHA, calculated as the lymphocyte-monokine interaction (LM) index, was determined in the micr ocultures of PBMC isolated from the blood of healthy donors or of patients with acute tonsillitis. The values of LM indices were compared with the rat ios of IL-1ra/IL-1 beta concentration estimated by enzyme-linked immunosorb ent assay method in the culture supernatants. The influences of exogenous I L-1 beta IL-1ra, anti-IL1ra antibodies and antibiotic cefaclor on the monok ine concentrations and on the values of LM index were tested. Results and conclusions: The results show that the level of lymphocyte resp onse to delayed stimulation with PHA (LM index) is inversely proportional t o the ratio of IL-1ra/IL-1 beta concentration in the culture. The low LM va lues at high IL-1ra/IL-1 beta ratios in PBMC cultures from healthy donors, reversed proportions found in patients' PBMC (acute tonsilitis), and the ce faclor-induced reduction of LM value with correlated increase of the IL-1ra /IL-1 beta ratio suggest that the LM assay may prove to be useful for immun odiagnostic purposes.