SETTLE Inflammation & Cytokine Study


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 treatments.

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 study.

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.

Endometrial Inflammation Study
Results of gving SETTLE at time of AI on Susceptible Mares (SM) at Diestrus


Click on graph to show larger image

SETTLE normalized the persistent,
post-breeding endometrial inflammation
in susceptible mares.