Our previous study demonstrated
mRNA and
protein expression of
peroxisome proliferator-activated receptor-g (
PPAR-g) in the immune system of weaned pigs. In this report, to test the hypothesis that activation of
PPAR-g in immune system modulates inflammatory response, and adrenal and somatotropic responses associated with immune challenge, we administered intraperitoneally
PPAR-g agonist and/or antagonist in weaned pigs subjected to Escherichia coli
lipopolysaccharide (LPS) challenge. Unexpectedly, we found that a single injection of the
PPAR-g agonist
rosiglitazone (given at 3 mg/kg
body weight 30 min before LPS injection) failed to block pro-inflammatory
cytokine production induced by LPS injection. Rather, plasma levels of
tumor necrosis factor-a (TNF-a) and
interleukin-6 (IL-6),
mRNA abundance of TNF-a in thymus, spleen, mesenteric lymph node and peripheral white blood cells,
mRNA abundance of
IL-6 in thymus,
protein levels of TNF-a in spleen and mesenteric lymph node, and
protein levels of
IL-6 in spleen and mesenteric lymph node, were elevated beyond the levels in control pigs injected with LPS. Furthermore,
rosiglitazone potentiated the increase of plasma
cortisol and
prostaglandin E(2) concentrations, and the decrease of plasma
insulin-like growth factor-1 concentration induced by LPS injection. Co-administration of the
PPAR-g antagonist
bisphenol A diglycidyl ether (given 30 mg/kg
body weight) 30 min prior to treatment with
rosiglitazone antagonized the effect of the
PPAR-g agonist, indicating a
PPAR-g-dependent effect. Our data indicate that
ligand-induced activation of
PPAR-g does not ameliorate but enhances pro-inflammatory
cytokine production, and further potentiates the adrenal and somatotropic changes in weaned pigs subjected to E. coli LPS challenge, which suggests that
PPAR-g activation may not be useful, but potentially harmful, in the treatment of immune challenge in livestock. Our results raise doubts about the prevalently accepted anti-inflammatory role for
PPAR-g activation.