|Reinhardt, Timothy - Tim|
Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/29/1997
Publication Date: N/A
Citation: Interpretive Summary: In the body, vitamin A is converted to biologically potent compounds referred as as retinoic acids. Studies using rodents, humans, and, more recently, cattle suggest that the retinoic acids can enhance the function of the immune system with beneficial effects on disease resistance. Scientists in our research unit have found that the blood levels of a specific form of retinoic acid, referred to as 9,13-di-cis-retinoic acid, are unusually elevated in cows which have recently given birth and in colostrum-fed calves. The biological significance of this form of retinoic acid is not known. The present study evaluated the effects of 9,13-di-cis-retinoic acid on the proliferation and function of a population of immune cells, referred to as mononuclear leukocytes, which are responsible for the recognition and destructiion of foreign substances and infectious agents (i.e., bacteria and viruses) that enter the body. Results from this study suggest that this form of retinoic acid, at concentrations seen in the blood, has negligible effects on the function and proliferation of this population of immune cells. Although the 9,13- di-cis-retinoic acid was ineffective, the discovery of a beneficial compound will allow development of drugs to improve the animal's immune system and help prevent or reduce the severity of diseases such as mastitis, diarrhea, and pneumonia.
Technical Abstract: The predominant isomer of retinoic acid in the plasma of dairy cows during the periparturient period is 9,13-di-cis-retinoic acid. Because retinoic acids influence the activity of cells in a variety of tissues, including the immune system, the potential for this isomer to modulate the bovine immune system in the periparturient period must be considered. The present study examined the in vitro effects of 9,13-di-cis-retinoic acid on the reactivity and phenotype of blood mononuclear leukocytes from antigen-sensitized, nongravid Holstein heifers with naturally low plasma concentrations of 9,13-di-cis-retinoic acid. In this system, 9,13-di-cis- retinoic acid approximating the highest plasma concentrations occurring in vivo during the periparturient period had no effect on DNA synthesis, secretion of interleukin-2 or interferon-gamma, or secretion of Ig by unstimulated cultures or cultures stimulated with mitogen (pokeweed mitogen) or antigen (ovalbumin). The composition of unstimulated and stimulated mononuclear leukocyte populations, based on percentages of specific cell types present, was unaffected by 9,13-di-cis-retinoic acid at the physiologic concentration of 10**8 M. 9,13-Di-cis-retinoic acid did not affect the actual number of cells in unstimulated cultures and cultures stimulated with antigen, but did cause a moderate reduction in the number of cells, primarily CD4+ lymphocytes, in mitogen-stimulated cultures. Overall, these results suggest that the elevated concentration of 9,13-di-cis-retinoic acid in maternal plasma may have a negligible effect on the reactivity and phenotype of cells comprising the circulating mononuclear leukocyte population.