Adrenocorticotropin stimulates natural killer cell activity

Area of Science:

• Immunology
• Endocrinology
• Animal Science

Background:

• Central corticotropin-releasing hormone (CRH) influences natural killer (NK) cell activity, separate from its role in the hypothalamic-pituitary-adrenal (HPA) axis.
• The direct impact of adrenocorticotropic hormone (ACTH) on NK cell cytotoxicity in pigs requires further investigation.

Purpose of the Study:

• To investigate the effect of ACTH on NK cell and interleukin-2 (IL-2)-activated NK cell cytotoxicity in pigs.
• To explore the relationship between ACTH administration, cortisol levels, and NK cell activity in a porcine model.
• To examine the influence of ACTH administration timing on NK cell activity within the context of circadian rhythms.

Main Methods:

• Porcine lymphocytes were cultured in vitro with ACTH, or pigs received intravenous (iv) or intramuscular (im) ACTH administration.
• NK and IL-2-stimulated NK cytotoxicity against K-562 target cells was measured.
• Serum cortisol levels and NK cytotoxicity were assessed at various time points after ACTH or vehicle administration, considering diurnal variations.

Main Results:

• In vitro ACTH had no direct effect on NK or IL-2-stimulated NK cytotoxicity.
• In vivo ACTH administration (iv or im) significantly elevated NK and IL-2-stimulated NK cytotoxicity in pigs, despite cortisol levels returning to baseline.
• Morning ACTH administration prevented the normal diurnal decline in NK cytotoxicity, while evening administration showed a less significant increase.

Conclusions:

• Exogenous ACTH enhances NK cell cytotoxicity in pigs through an indirect mechanism, potentially involving cortisol-mediated suppression of central CRH.
• The timing of ACTH administration influences its effect on NK cell activity, with greater impact during periods of normally low NK cytotoxicity.
• These findings highlight a complex interplay between the HPA axis, circadian rhythms, and immune function in pigs.