Abstract
An acute phase response induced by Gram-negative bacteria can reduce pregnancy rate. Early pregnant ewes were used to monitor effects of lipopolysaccharide (LPS), an endotoxin in the outer cell membrane of Gram-negative bacteria, on acute phase/innate immunity response. In Exp. 1, mixed breed ewes were assigned to receive either LPS or LPS and flunixin meglumine, an inhibitor of prostaglandin synthetase, intravenously on day 5 after mating. In Exp. 2, mixed breed ewes were assigned to receive an intravenous injection on day 5 after mating of either saline, LPS, recombinant human tumor necrosis factor (TNF)-α or LPS after pretreatment with dexamethasone. Pregnancy was diagnosed ultrasonographically on d 25, and live births were recorded at parturition. Challenge with LPS induced acute phase responses (fever, mucosal responses, lethargy and increased serum TNF, haptoglobin and serum amyloid A) and decreased pregnancy rates. Predictably, flunixin meglumine attenuated fever but did not increase pregnancy rate in LPS-treated ewes. Similarly, exogenous TNF alone induced mucosal and serum amyloid A responses but did not affect pregnancy. Pre-treatment with dexamethasone blocked fever and mucosal and lethargic responses and attenuated increases in TNF and haptoglobin but did not ameliorate LPS-induced pregnancy loss. In summary, acute challenge with LPS mimics bacterial-induced pregnancy losses in early pregnant ewes. Although pretreatment with dexamethasone decreased clinical signs and some innate immune responses, neither it nor flunixin meglumine prevented LPS-induced pregnancy loss. That exogenous TNF alone did not promote pregnancy loss indicates that other cytokines also contribute to LPS-induced embryonic loss.
Highlights
IntroductionThe early immune response associated with bacterial challenges likely compromises establishment or early maintenance of pregnancy [2] [3]
Jugular concentrations of tumor necrosis factor (TNF) in ewes pre-treated with flunixin meglumine increased in comparable fashion to ewes treated only with LPS increasing from 0.13 ng/ml to a peak of 1.08 ng/ml (Figure 2(a))
In previous studies [7] [8] [9], mated ewes inoculated with peptidoglycan-polysaccharide or killed Streptococcus pyogenes, a gram-positive bacterium, showed typical physical and immunological changes including transient increases in serum concentrations of TNF, cortisol, HP and serum amyloid A (SAA) after bacterial challenge and increased serum concentrations of PGFM and reduced serum concentrations of progesterone, which were associated with decreased early embryonic survival
Summary
The early immune response associated with bacterial challenges likely compromises establishment or early maintenance of pregnancy [2] [3]. Both lipopolysaccharide (LPS), a component of Gram-negative bacteria, and peptidoglycan-polysaccharide, a component of Gram-positive bacteria, have been used to investigate the mechanism by which bacterial infection leads to early embryonic failure. Injection of peptidoglycan-polysaccharide on day 5 after mating resulted in acute phase response [APR: fever and increased jugular plasma concentrations of TNF, haptoglobin (Hp) and serum amyloid A (SAA)], decreased concentrations of progesterone on days 14 and 21 and interfered with establishment of early pregnancy [9]
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