Nonphotic stimuli alter a day-night rhythm of allograft rejection in gulf killifish.
ABSTRACT The influence of environmental stimuli on a daily rhythm of immune activity during scale allograft rejection was investigated in gulf killifish, Fundulus grandis. Although melanophore destruction in the grafts is largely restricted to the scotophases in killifish held on 12 h daily photoperiods (LD 12:12), timed daily netting (tank-transfer "stress"), thermoperiods (from 20 degrees to 30 degrees C for 4 or 12 h), and feeding altered the expression of this rhythm. Melanophore breakdown peaked 0-12 h after netting or thermoperiod onset and 12-24 h after feeding, whether the fish were exposed to these nonphotic daily stimuli at the onset or offset of 12-h photoperiods. In fish held under continuous light and pretreated with these daily stimuli, 24-h immune activity rhythms persisted in the altered phases for several days after the daily treatments were stopped. These findings suggest that a daily rhythm of immune activity may have adaptive significance in fish.
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ABSTRACT: In the present study, we investigated the time-dependent interactive effects of daily injections of prolactin (PRL) and corticosterone (CORT) on the activation of lymphocyte function and inhibition of tumor growth in vivo in mice. BALB/c mice were injected subcutaneously with EMT-6 fibrosarcoma cells (a murine connective tissue tumor cell derived from mammary gland), and then different groups of animals were treated with PRL (1 microg/g body weight [BW] ip) at Oh, 4h, 8h, 12h, 16h, or 20h after CRT (1 microg/g BW ip) daily for 10 days. Different control groups were vehicle treated or treated with either hormone alone. Mice were kept in constant light 1 week before and during injections and in a 14:10 light-dark cycle thereafter. Tumor progression was monitored for up to 21 days after the cessation of treatment, and thereafter spleen lymphocytes were harvested and tested for mitogen-triggered proliferation. Prolactin administration at 8h or 16-20h after corticosteroid treatment reduced tumor volume by 77% and 49%, respectively, relative to vehicle-treated controls. Other time relations of hormone treatment were ineffectual. Further studies indicated that the immunosuppressant cyclosporin A (CSA) substantially stimulated tumor growth; this effect was completely abrogated by a simultaneous 8h related hormone treatment. How ever, the 8h hormone treatment was ineffective in inhibiting tumor growth in T-cell-deficient nude mice. Spleen lymphocytes from tumor-bearing (TB) mice showed an elevated basal proliferative capacity stimulated by concanavalin A (ConA; a stimulus for T-cell proliferation) and lipopolysaccharide (LPS; a stimulus for B-cell proliferation) compared to non-TB mice. Spleen lymphocytes from TB mice treated with CORT and PRL at 8h intervals exhibited an increased spontaneous (as well as LPS- and ConA- triggered) proliferation (by 104%, 48%, and 70%, respectively) compared with vehicle control TB mice. Fluorescence-activated cell sorting (FACS) analysis of splenocytes from hormone-treated animals indicated a 34-100% increase in the CD4+ (e.g., T helper cell) population. Treatment of animals with either hormone alone did not inhibit tumor growth or stimulate immune function relative to vehicle controls. The daily rhythms of plasma PRL, CORT, and thyroxine were all substantially altered by the presence of tumor in these mice. These results indicate that appropriately timed daily treatment of PRL and CORT can attenuate tumor growth, in part, via activation of antitumor immune mechanisms. Collectively, these data suggest that circadian neuroendocrine activities must be temporally organized appropriately to inhibit tumor growth.Chronobiology International 06/1999; 16(3):315-33. DOI:10.3109/07420529909116861 · 2.88 Impact Factor
Developmental & Comparative Immunology 03/1997; 21(2):151-151. DOI:10.1016/S0145-305X(97)88624-7 · 3.71 Impact Factor
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ABSTRACT: The length of time required to reject scale allografts was examined in groups of male gulf killifish (Fundulus grandis) treated daily with either 4-h thermoperiods (daily intervals of 30°C during a 20°C continuum), single meal feedings, or net-chasing disturbances at one of six different times after the onset of daily photoperiods (LD 12:12 or LD 14:10). Scale allograft survival varied by 30–60% in each timed stimulus experiment as a function of the time of day when the stimulus was provided. The phase relationship between two circadian neuroendocrine oscillations, previously proposed to regulate physiologic and behavioral conditions in gulf killifish, may have important influences on the immune system as well. The phase of one oscillation is thought to be set by the daily photoperiod, and the other is preferentially set by the nonphotic daily stimulus. © 1995 Wiley-Liss, Inc.Journal of Experimental Zoology 05/1995; 272(1):46 - 53. DOI:10.1002/jez.1402720106