Biology Reference
In-Depth Information
pathway
[97,98]
. Membrane-bound sphingomyelinase activity changes in nerve cells
and immunocompetent cells in response to stress. Glucocorticoid hormones modify
IL-1 signal transduction via the sphingomyelin pathway
[99]
.
The response to infection and severe injury, which is analogous to the stress
response, is now known as the
acute phase response
(APR)
[100]
. Major contribu-
tions were made to the subject of cytokine signaling of the brain during APR by
McCann et al.
[101]
and Bartfay and co-workers
[102]
. Fever is a hallmark of APR;
Blatteis and colleagues rose to excellence in fever research
[103]
.
2.5.5 Biological Rhythms in Neuroimmune Regulation
Living organisms have the capacity to adapt to their environment. In general, daily
(diurnal or circadian) and seasonal (circannual) adaptations are distinguished.
Melatonin, a pineal hormone, is a key mediator of biological rhythms. Maestroni
and co-workers
[104]
demonstrated first that melatonin is a major immunoregulatory
hormone. The circadian organization of the immune response is discussed in this vol-
ume by Esquifino and Cardinali
[105]
.
2.5.6 Pavlovian Conditioning of Immune Reactions
An original approach is represented by the studies of Ader et al.
[106-109]
, who
investigated the role of Pavlovian conditioning in the suppression of immune reac-
tions. These studies, which used the immunodepressant drug cyclophosphamide (CP)
as the unconditioned stimulus, demonstrated that it is possible to suppress humoral
and cell-mediated immune responses if CP treatment is paired with a conditioning
stimulus. Conditioning could also be used to influence immunopathological pro-
cesses. Ader chose an exceptionally appropriate model, which made it possible to
reproduce the pharmacological effect of CP with the conditioned reflex ultimately
resulting in immunosuppression. A key contributor to this area of research is Reginald
Gorczynski
[110]
.
2.5.7 Stress and Immunity
An enormous number of publications deal with the clinical relevance of stress to
disease processes, which was first pointed out by Solomon
[15,16]
. Glaser and co-
workers
[111]
contributed significantly to stress research, especially with regard to
its clinical applications. Stress is known to alter the neuroimmune relationships in the
body
[88,89]
. The hypothalamus-pituitary-adrenal axis (HPA) is activated not only
by IL-1, but also by IL-6 and TNF, the levels of which increase with stress
[112]
.
Glucocorticoid hormones, which are indispensable components of stress response,
suppress the adaptive immune system by inhibiting the secretion of such cytokines
as IL-1, -2, -3, -5, -6, -8, -12, and others
[113,114]
; by influencing the expression of
cytokine receptors on immunocompetent cells
[113,115]
; and by inducing apoptosis
