Biomedical Engineering Reference
In-Depth Information
subset (Coffman
2006
) . Thus, IFN- g and IL-4 do
not directly inhibit differentiated Th1 or Th2 cells,
but they inhibit by blocking the differentiation of
these subsets from naïve precursors. The IFN-g
has been shown to inhibit Th2, whereas IL-4
and IL-10 inhibit Th1 (Coffman
2006
) , and the
IL-12 favours Th1 and has no effect on Th2
(Constant and Bottomly
1997
) . However, it may
be specified that none of the cytokines specific to
one particular subset are exclusive products of
Th cells because other leucocytes can also con-
tribute to Th1- or Th2-type responses (Mosmann
and Sad
1996
) .
Cytokines released upon activation of the
immune system in response to stress stimulate
the HPA axis and increase peripheral levels of
glucocorticoids and catecholamines, which in
turn suppress the synthesis and release of cytok-
ines. Glucocorticoids inhibit a large number of
cytokines, including IL-4, IL-5, IL-6, IL-12,
IFN-g and tumour necrosis factor-a (Wiegers and
Reul
1998
; Richards et al.
2001
; Sapolsky et al.
2001
). However, not all cytokines are suppressed
by glucocorticoids and IL-10 secretion is
increased by glucocorticoids (Blotta et al.
1997
;
Richards et al.
2001
), whereas IL-1, IL-4 and
IL-6 act synergistically with glucocorticoids in
humans (Wiegers et al.
2005
) . The glucocorti-
coids enhance IL-4 production (Wu et al.
1991
;
Blotta et al.
1997
). Also, IL-4 is enhanced by
IL-12, but glucocorticoids inhibit IL-12 (Wu
et al.
1998
; Elenkov et al.
2000
) . The inhibition
of cytokines by glucocorticoids is regarded as
a protective mechanism that prevents over-
shooting of the immune defences. In general,
glucocorticoids inhibit proinflammatory cytokine
synthesis or induce the cytokines that have immu-
nosuppressive potential (Wiegers et al.
2005
) .
production and neutrophil function (Blecha and
Baker
1986
; Salak et al.
1993
) . A high dose of
dexamethasone has been found to profoundly
increase the number of circulating neutrophils in
heifers but inhibited neutrophil cell surface
marker expression (Weber et al.
2001
) . The num-
ber of apoptotic cells increased, whereas the
number of proliferating cells decreased in calves
receiving dexamethasone injections twice daily
for 4 days (Norrman et al.
2003
) , thus leading to
an increase in the ratio of apoptotic cells to pro-
liferating cells. In these same calves, T-cells were
observed to increase, but B-cells decreased.
Activation of the HPA axis by administering
exogenous ACTH, cortisol or by blocking corti-
sol synthesis has been used to investigate the
effects of cortisol on immune function. In pigs,
administration of an intravenous bolus of ACTH
caused an increased natural killer (NK) activity
and IL-2-stimulated NK activity (McGlone et al.
1991
), whereas an ACTH injection suppressed
neutrophil cellular function in Japanese Black
steers (Ishizaki and Kariya
1999
) . A pharmaco-
logically induced, threefold increase in plasma
cortisol concentration via cortisol injection was
observed to have no effect on NK cytotoxicity,
but an infusion of 400 mg of cortisol resulted in
reduced NK activity at 1 h post injection, but not
at 2 h (Salak-Johnson et al.
1996
) . Blocking cor-
tisol synthesis by feeding metyrapone to pigs
resulted in low plasma cortisol concentrations
and reduced NK cytotoxicity (Salak-Johnson
et al.
1996
). Central injection of CRF has been
observed to decrease NK cell activity in rodents
(Irwin et al.
1990
), marginal reduction in pigs
was observed, but neutrophil chemotaxis was
significantly suppressed (Salak-Johnson et al.
1997
) by central CRF injection. Administration
of central CRF resulted in reduced concanavalin-
A (Con A)-induced proliferation in pigs (Johnson
et al.
1994
) but had no effect on phytohaemag-
glutinin (PHA)-induced proliferation (Salak-
Johnson et al.
1997
) .
Prior to the administration of LPS (0.5 m g/kg
body weight), temperamental bulls had higher
cortisol and epinephrine concentrations as com-
pared to calm or intermediate bulls. Cortisol con-
centrations increased following LPS administration
4.2
Effect of Stress Hormones
Stress hormones released in response to activa-
tion of the HPA axis (CRF, ACTH and cortisol)
have been observed to have an effect on the
immune system. The incubation of cattle and
porcine immune cells with cortisol has been
shown to suppress lymphocyte proliferation, IL-2
