Abstract

There is a well established bi-directional link between the mammalian endocrine and immune systems. These finely tuned interactions are required for the survival and health of an individual and are regulated by circulating hormones and cytokines, which are in turn influenced by body condition, reproductive status, and stress levels. Hormones have significant interaction with the immune system with both immuno-enhancing and suppressive effects being reported (Dhabhar, 2000).

We examined the effects of artificial stress induced by a 5 μg/kg IM injection of Cortrosyn^TM (cosyntropin; Amphastar Pharmaceutical, Inc), a synthetic ACTH, on total and differential leukocyte counts, serum cortisol levels, blood chemistries and in vitro lymphocyte blastogenic function in seven harbor seal pups under two diet regimes. We hypothesized that: 1) A dose of 5 μg/kg Cortrosyn^TM would elicit a significant increase in serum cortisol levels indicative of an acute stress response; 2) The acute stress response would impact immune function; 3) Harbor seals on a low lipid diet (LF) will have an altered endocrine and immune function compared to cohorts on a high lipid diet (HF).

All pups consumed a mixed diet comprised of herring (30%), pollock (30%), capelin (30%), and squid (10%). Four seals were on a HF diet (16 % lipid herring) while the remaining three were on a LF diet (< 6% lipid herring). Serial blood samples were collected at time of catheter placement, 0 minutes and at 60, 90, 165, 240 minutes after ACTH administration. The final blood sample was collect 26 hrs after Cortrosyn administration.

Serum cortisol levels peaked at 165 minutes (20.31 ± 8.47 ng/ml) compared to time 0 (2.84 ± 1.03 ng/ml) and remained significantly elevated 26 hrs post injection (9.67 ± 2.73 ng/ml; p=0.018, Wilcoxon matched-pairs signed rank test). A stress leukogram was present in all pups with the largest change observed in the 240 min sample with total leukocyte count increasing by 10.0% ± 3% with a consistent neutrophilia (increasing by 18.0% ± 10.1%) and lymphopenia (decreasing by 28.1% ± 17.3%) in all pups. While there was still a significantly elevated total leukocyte count (p=0.028, Wilcoxon matched-pairs signed rank test) at 26 hrs post blood sample, the lymphopenia had reversed and the lymphocyte count had significantly increased from 1,966 ± 659 at time 0 to 2,743 ± 433 at 26 hrs (p=0.018, Wilcoxon matched-pairs signed rank test).

Preliminary results indicate: 1) The administration of 5 μg/kg Cortrosyn induced an acute stress response in harbor seal pups; 2) A significant increase in serum cortisol levels preceded the development of the stress leukogram; 3) The acute stressor had significant impacts on the immune system, as evidenced by altered leukograms at the 240 min and 26 hrs blood samples.

These results are further evidence that changes in circulated hormone levels impacts immune function.

References

1.  Dhabhar FS (2000) Acute stress enhances while chronic stress suppresses skin immunity. Annals of the New Your Academy of Sciences. 876-893.