Biomedical Engineering Reference
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phosphatidylinositol 3-kinase and p38 mitogen-
activated protein kinase pathways (Kinjyo et al.
2002 ). With changes in PRL concentration in
plasma, it is plausible that effects of heat stress
on immune function may be mediated through
the PRL-signalling pathway and lymphocyte
cytokine production.
The intracellular proteins SOCS-1 and
SOCS-3 inhibit signal transduction of type I and
type II cytokine receptors (such as PRL-R), pos-
sibly through action at the level of receptors and
JAKs; however, CIS and SOCS-2 act mainly by
competition with STAT factors for recruitment to
activated receptor complexes (Dalpke et al. 2008 ) .
Lymphocytes from cows which were provided
with cooling had lower expression of SOCS-1
and SOCS-3 mRNA. The protein SOCS-1 is an
essential negative regulator for T-cell activation
by dendritic cells and for maintaining immuno-
logical tolerance by restricting CD8 + T-cell pro-
liferation. Thus, low expression of SOCS-1 may
enhance JAK2 activity, thereby promoting cell
proliferation (Yoshimura et al. 2007 ) . The lympho-
cytes of cooled cows proliferate more than those
of heat-stressed cows and expressed less SOCS-1
mRNA. However, there was no effect of heat
stress on mRNA expression of SOCS-2 or CIS.
In addition, HSPA5 mRNA, which encodes a
member of the HSP70 protein family, was upreg-
ulated in lymphocytes from heat-stressed cows at
+20 day relative to calving compared to cooled
cows; however, expression was not affected dur-
ing the dry period in which heat stress was
imposed. Likewise, no effect of summer heat
stress was reported in the expression of HSP70 in
lymphocytes isolated from grazing beef cattle
(Eitam et al. 2009 ). In vitro data suggest that
HSP70 require temperatures above 42 °C for
activation (Williams et al. 1993 ) . The metabolic
stress of lactation might also play a role in lym-
phocyte HSPA5 mRNA expression. In fact,
increased expression of HSP70 has been shown
to be protective of cells to metabolic stress
(Williams et al. 1993 ) . Large farm animals
exposed to heat stress conditions have differen-
tial induction of serum HSP70 levels compared
with lymphocytes treated in vitro. Furthermore,
both hot-humid and dry-heat stressors effectively
induce HSP70 in lymphocytes (Mishra et al.
2011 ). Nonetheless, hot-humid condition caused
lesser increase in HSP70 concentration than hot-
dry. Thermal stress causes increased HSP70 syn-
thesis both in isolated lymphocytes as well as in
intact animals. Increase in serum HSP70 level to
either dry-hot or hot-humid stress substantially
differs with isolated in vitro treatments of stress
and should be considered while evaluating dif-
ferent effects of stressors. However, increase in
HSP70 as a thermo-adaptive response does not
serve immune protection at physiological level
(Mishra et al. 2011 ) .
In terms of cytokine production, lymphocytes
isolated from heat-stressed cows also produced
less TNF-a compared to the cows provided with
cooling. It has been reported that SOCS-1 inhibits
TNF-a secretion (Kinjyo et al. 2002 ) . In contrast,
CIS can be induced by TNF-a (Starr et al. 1997 ).
Indeed, CIS mRNA expression in lymphocytes
from cooled cows was numerically greater (120%
vs. 83%; SEM = 24%; P = 0.30) than in those of
heat-stressed cows. IFN-g and IL-4 secretion
from the lymphocytes did not differ between
treatments. Lower IFN- g and IL-4 production
from the heat-stressed lymphocytes were
expected, as SOCS-1 inhibits both IFN-g and
IL-4 (Dalpke et al. 2008 ) . However, IL-6 secre-
tion did not differ between lymphocytes from
heat-stressed and cooled cows. PRL-R and SOCS
mRNA are differentially expressed between lym-
phocytes isolated from both group of cows. The
greater PRL-R and lower SOCS-1 and SOCS-3
mRNA expressions in lymphocytes from cooled
cows were associated with greater lymphocyte
proliferation and may be a mechanism whereby
cooling improves immune cell function. In addi-
tion, the increased TNF-a cytokine production of
lymphocytes of cool cows provides evidence of
cell communication to mount an appropriate reg-
ulated immune response (Amaral et al. 2010 ) .
7
Nutrition and Immunity
Attempts are being made to decrease or eliminate
the use of antimicrobials in livestock production
system due to a growing concern that existing pro-
duction practices may lead to an increase in the
number of antibiotic-resistant human pathogens
 
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