It was postulated that frequent pulses of cortisol such as might be induced
by a repeated or chronic stressor, could induce immune suppression and tha
t the effect would be greater than in animals subjected to less frequent in
creases. Four groups of nine adult Scottish Blackface ewes were infused for
14 d with saline or hydrocortisone hemisuccinate (cortisol) delivered cont
inuously or in pulses. Plasma concentrations of cortisol were significantly
elevated (to between approximately 100 and 1000 nmol/liter; P < 0.001) for
about 30 or 75 min after infusion of pulses of hydrocortisone hemisuccinat
e at intervals of 1 hr (P1) or 6 hr (P6), respectively. In animals continuo
usly infused (CI), they were consistently elevated (P < 0.001), compared wi
th concentrations in control animals infused with saline only (S), to appro
ximately 1000 nmol/liter or more. Antibody production in response to ovalbu
min injection was not affected by any of the infusion regimes. At Days 10,
24, and 31 after injection of ovalbumin and initiation of the infusion, rat
es of multiplication of unstimulated lymphocytes, in vitro, were greater (P
< 0.05) in P6 animals than in saline-infused, control animals and this res
ulted in a reduction in the stimulated lymphocyte response. As a consequenc
e of the increased basal lymphocyte activity, after Day 0, the corrected, s
timulated lymphocyte response of P6 animals was consistently below that of
controls (P < 0.05 at Day 24). Both mean basal and stimulated lymphocyte ac
tivities in CI and P1 animals were similar to those of controls. The gamma
interferon (IFN-gamma) response was generally small and not affected by tre
atment. It is concluded that large, relatively infrequent increases in circ
ulating cortisol concentrations can modify the cell mediated immune respons
e such that the response to a specific antigen challenge is compromised but
smaller, more frequent pulses had no effect. Elevated cortisol concentrati
ons per se did not have a significant inhibitory effect on the immune syste
m. (C) Elsevier Science Inc. 1999.