Inflammation & Cytokine Responses 2-5,7,8
SETTLE accelerates the resolution of
persistent, post-breeding endometrial
inflammation in susceptible mares.
A post-breeding inflammatory reaction to sperm,
microorganisms and cellular detritus is a normal physiological reaction
by the mare’s endometrium. Fertile mares are able to clear this mild
inflammation within 48 hours. These mares are designated as
endometritis Resistant Mares (RM). Mares that fail to resolve the
inflammatory processes will fail to conceive and are recognized as
endometritis Susceptible Mares (SM). Whereas most acute uterine
infections either recover spontaneously or with appropriate therapy,
chronic post-breeding endometritis will often persist despite rigorous
Endometrial biopsy studies in SM demonstrated that a single dose of
SETTLE (administered intravenously at the time of artificial
insemination with dead sperm) significantly decreased the numbers of
polymorphonuclear-leukocytes (PMN) and the edematous reaction.2
From the Ayacucho PMSG-production herd, 51 mares were identified by
intrauterine challenge with 106 cfu Streptococcus zooepidemicus during
estrus and were then divided into SM or RM animals by their ability to
clear the infection by 72 hours and then conceive to natural breeding.
Eight mares from each group were then selected an inflammatory response
Endometrial PMNs, plasma acute phase proteins (APP) and plasma
cytokines (IL-1b, IL-6 and
TNF-a) were evaluated at estrus and diestrus
(seven days after ovulation) to determine the baseline inflammatory
responses in both SM and RM. All animals were then challenged with 5 x
108 dead sperm in Kenney’s extender to assess sperm-induced
inflammation. Mares were sampled at estrus, 24 hours after
insemination, and diestrus. At the next estrus, the same mares were
treated with intravenous SETTLE immediately after AI with dead sperm.
Susceptible mares demonstrated a statistically significant
sperm-induced inflammation (PMN and APP) (p<0.05) and cytokine response
(p<0.01) at estrus and diestrus compared with resistant mares.
Following SETTLE treatment, susceptible mares
and resistant mares demonstrated equivalent responses at diestrus
with PMN/400x being
less than 5.
SETTLE normalized the persistent, post-breeding
endometrial inflammation in susceptible mares.