In a rat model of intestinal ischaemia and reperfusion injury, PDE4 inhibition with rolipram partially reversed local and remote injuries but was less effective than anti-TNF-alpha anti-serum.
Does PDE4 or TNF-alpha inhibition reduce local and remote injuries following intestinal ischaemia and reperfusion injury in rats?
In a rat model of intestinal ischaemia/reperfusion injury, TNF-alpha inhibition was more effective than PDE4 inhibition at protecting against local and remote tissue injuries and preventing lethality.
The effects of phosphodiesterase (PDE)4 and TNF-alpha inhibition were assessed on the local and remote injuries following intestinal ischaemia and reperfusion (I/R) injury in rats. 2. The PDE4 inhibitor rolipram dose-dependently (1 - 10 mg kg(-1)) suppressed the local (intestine) and remote (lung) increases in vascular permeability and neutrophil recruitment following mild I/R injury. SB207499 (ariflo), a structurally-distinct PDE4 inhibitor, also suppressed the injuries following mild I/R injury. 3. In a severe model of I/R injury, treatment with rolipram (10 mg kg(-1)) partially reversed the local and remote increases in vascular permeability, neutrophil recruitment, intestinal haemorrhage and intestinal LTB(4) concentrations. The anti-TNF-alpha anti-serum was more effective than rolipram at inhibiting local and remote injuries and prevented the lethality associated with severe I/R. 4. Rolipram and anti-TNF-alpha prevented the increase in the concentrations of TNF-alpha in the lung and intestine, but rolipram only partially inhibited the elevation of this cytokine in serum. Rolipram had little effect on the increases of IL-1 beta concentrations in lung and serum, whereas treatment with anti-TNF-alpha markedly increased the concentration of this cytokine. Concentrations of IL-10 rose significantly in the lung and serum and these increases were blocked by rolipram or anti-TNF-alpha. 5. The capacity of PDE4 inhibitors to block the recruitment of neutrophils into tissues, the production of LTB(4) and of the pro-inflammatory cytokines TNF-alpha, IL-1 beta and IL-6 appear to underlie their anti-inflammatory effects in our model of I/R injury. Overall, PDE4 inhibition was less effective than inhibition of TNF-alpha for protection against I/R injury.
Souza et al. (Thu,) conducted a other in Intestinal ischaemia and reperfusion injury. PDE4 inhibitors (rolipram, SB207499) and anti-TNF-alpha anti-serum vs. Untreated I/R injury was evaluated on Local and remote injuries (vascular permeability, neutrophil recruitment, intestinal haemorrhage, lethality). In a rat model of intestinal ischaemia and reperfusion injury, PDE4 inhibition with rolipram partially reversed local and remote injuries but was less effective than anti-TNF-alpha anti-serum.