24-HOUR RHYTHMS IN IMMUNE-RESPONSES IN RAT SUBMAXILLARY LYMPH-NODES AND SPLEEN - EFFECT OF CYCLOSPORINE

Twenty-four-hour variations in cellularity, lipopolysaccharide (LPS)- and concanavalin A (Con A)-induced cell proliferation. and natural kil ler (NK) activity were examined in submaxillary lymph nodes and spleen of rats injected with Freund's complete adjuvant or its vehicle and k ept under light from 08:00 to 20:00 h daily. A significant daily varia tion in cellularity was detected, exhibiting maxima at 09:00 h in subm axillary lymph nodes (nonimmunized and immunized rats) and at 13:00 h in spleen (immunized rats only). Submaxillary lymph node LPS- and Con A-mitogenic effect displayed maximal activity during daytime (peak at 13:00-17:00 h). In spleen, the maxima for 24-h rhythm in LPS-induced c ell proliferation and MC activity occurred at midnight and at early mo rning (09:00 h), respectively. Con A-induced spleen cell proliferation peaked at midday in nonimmunized rats only. Injection of the immunosu ppressive drug cyclosporine decreased Freund's adjuvant-induced augmen tation of LPS and Con A mitogenic effect in both tissues and diminishe d spleen cell number. Cyclosporine blunted circadian rhythms in submax illary lymph node Con A response and cell number, while it shifted the maximum in LPS effect to peak at 01:00 h. Cyclosporine also suppresse d the circadian changes in LPS- and Con A-induced spleen cell prolifer ation, but not those found in NK activity. The results indicate the ex istence of 24-h rhythms in immune responses of rat submaxillary lymph nodes and spleen with maxima at different times of the day and that we re significantly affected by cyclosporine injection. (C) 1996 Academic Press, Inc.