Effects of pulsed or continuous infusion of cortisol on immune function in sheep

It was postulated that frequent pulses of cortisol such as might be induced by a repeated or chronic stressor, could induce immune suppression and that the effect would be greater than in animals subjected to less frequent increases. Four groups of nine adult Scottish Blackface ewes were infused for 14 d with saline or hydrocortisone hemisuccinate (cortisol) delivered continuously 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 hemisuccinate at intervals of 1 hr (P1) or 6 hr (P6), respectively. In animals continuously infused (CI), they were consistently elevated (P < 0.001), compared with concentrations in control animals infused with saline only (S), to approximately 1000 nmol/liter or more. Antibody production in response to ovalbumin 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, rates of multiplication of unstimulated lymphocytes, in vitro, were greater (P < 0.05) in P6 animals than in saline-infused, control animals and this resulted in a reduction in the stimulated lymphocyte response. As a consequence of the increased basal lymphocyte activity, after Day 0, the corrected, stimulated lymphocyte response of P6 animals was consistently below that of controls (P < 0.05 at Day 24). Both mean basal and stimulated lymphocyte activities in CI and P1 animals were similar to those of controls. The gamma interferon (IFN-gamma) response was generally small and not affected by treatment. It is concluded that large, relatively infrequent increases in circulating cortisol concentrations can modify the cell mediated immune response such that the response to a specific antigen challenge is compromised but smaller, more frequent pulses had no effect. Elevated cortisol concentrations per se did not have a significant inhibitory effect on the immune system.