Biology Reference
In-Depth Information
IL-11, IL-12, leukemia inhibitory factor, granulocyte macrophage colony-stimulating
factor, oncostatin, and stem cell factor. These were found to affect the HPA axis and
the release of other pituitary hormones
[40]
. These CTKs represent macrophages,
T cells, NK cells, mast cells, bone marrow cells, and stem cells, which are members
of both the adaptive and innate immune systems. CTKs, which are produced after
cell activation during immune reactions or other (e.g., bone marrow) functions, sig-
nal the brain and endocrine organs directly or via sensory nerves.
There is compelling evidence indicating that cytokines fulfill physiological roles
not only in the immune system, but also in the CNS and in other tissues and organs.
Therefore, shared CTKs allow organ- and tissue-specific regulation. CTKs may also
inform the brain about immune activity, as well as about other physiological pro-
cesses (e.g., GM-CSF indicates granulocyte/macrophage production)
[25,41]
.
The ascending and descending signaling pathways elicited by IL-1 were inves-
tigated. The central network consists of ascending pathways that are triggered after
the transduction of IL-1 signals across the blood-brain barrier. Brainstem neurons,
primarily located in the area postrema, nucleus tractus solitarius, and ventrolateral
medulla, are the first central neurons recruited, and by direct and indirect pathways
converge on the paraventricular nucleus to initiate HPA axis responses. Descending
neuroimmune pathways from the paraventricular nucleus also transmit IL-1 signals
down to the brainstem cell groups and to thoracic spinal cord preganglionic neurons,
and via sympathetic projections innervate immune end organs such as the thymus
and spleen. The coordination of these neural networks in response to a systemic
immune challenge is important for the regulation of peripheral immune responses by
the brain
[42]
.
7.3.2 Neuroimmune Regulation of ADIM
Our initial observations on the immunoregulatory role of the pituitary gland revealed
that hypophysectomized (Hypox) young rats (100 g body weight) did not respond
to primary immunization with various antigens; the thymus, spleen, and bone mar-
row of these rats showed atrophy and lack of DNA and RNA synthesis. Humoral,
cell-mediated, and autoimmune reactions were inhibited. Replacement doses of pro-
lactin (PRL), growth hormone (GH), and also placental lactogen reversed these defi-
ciencies
[43-49]
. These findings have been confirmed by a number of laboratories.
However, it was also observed that PRL gene and receptor knockout mice remained
immunocompetent
[50,51]
. The explanation for these results is that GH was pres-
ent, and was equally capable of maintaining immunocompetence, in such knockout
animals. Additional observations also support the immunoregulatory role of GLHs.
For example, pituitary dwarf individuals are immunocompetent, as their PRL is nor-
mal
[52]
. Pit-1-deficient animals and humans have residual GLHs, which explains
their survival
[53,54]
. Newborn mice treated with PRL antibodies (or with ergoline)
became retarded and showed developmental abnormalities, and about 30% did not sur-
vive
[55]
. The dopaminergic agent bromocriptine inhibits PRL secretion and is immu-
nosuppressive
[56]
. The secondary antibody response is partially pituitary dependent
[47]
. Long-surviving Hypox rats have residual serum PRL (
40% of normal). If this
