Related Experiment Video
Updated: Jun 20, 2026
Visualizing Leukocyte Rolling and Adhesion in Angiotensin II-Infused Mice: Techniques and Pitfalls
Published on: January 4, 2018
Differential effects of rolipram on chronic subcutaneous inflammatory angiogenesis and on peritoneal adhesion in mice
Juliana B Mendes1, Monaliza A Rocha, Fernanda A Araújo
1Departments of Physiology and Biophysics and General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Abstract:
The specific PDE4 inhibitor (rolipram) has been shown to attenuate excessive accumulation/activation of inflammatory cells and fibroblasts and cytokine production in several pathological conditions through cyclic nucleotide modulation. Here, using the murine sponge model to induce chronic subcutaneous inflammatory response and to elicit the formation of intraperitoneal adhesions we explored the hypothesis that rolipram would exert beneficial effects on decreasing key components of both processes (inflammatory cell recruitment, angiogenesis, and deposition of extracellular matrix component). Two doses of rolipram (0.2 or 2 mg/kg/day) were administered orally for 7 days in groups of mice bearing either subcutaneous or intraperitoneal polyether-polyurethane implants. Rolipram was effective in inhibiting angiogenesis as assessed by hemoglobin content and VEGF levels in subcutaneous implants (about 40% with both doses) but failed to exert this activity in intraperitoneal implants. Conversely, accumulation of neutrophils and macrophages determined by measuring myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) activities intraimplant, respectively, was attenuated only in intraperitoneal implants by the treatment. Levels of TNF-alpha and MCP-1 were also determined and rolipram at both doses decreased the production of both cytokines in intraperitoneal implants. The levels of MCP-1 in the subcutaneous implants were not affected by the treatment. Fibrosis was evaluated by determining the amount of collagen and production of TGF-beta1 intraimplant. Both parameters were attenuated by rolipram. These results have shown differential sensitivity of proliferating tissues to PDE4 inhibitor indicating that this agent may be used to target inflammatory angiogenesis selectively.
Insights
Rolipram, a PDE4 inhibitor, showed differential effects on inflammatory responses. It inhibited angiogenesis in subcutaneous implants but reduced inflammatory cell accumulation and fibrosis in intraperitoneal implants.
Area of Science:
- Pharmacology
- Immunology
- Biomedical Engineering
Background:
- Phosphodiesterase 4 (PDE4) inhibitors modulate cyclic nucleotides, impacting inflammatory processes.
- Rolipram is a specific PDE4 inhibitor studied for its effects on inflammatory cell accumulation, fibroblast activation, and cytokine production.
- The murine sponge model is used to study chronic subcutaneous inflammation and intraperitoneal adhesion formation.
Purpose of the Study:
- To investigate the effects of rolipram on inflammatory cell recruitment, angiogenesis, and extracellular matrix deposition in subcutaneous and intraperitoneal inflammatory models.
- To determine if rolipram exhibits beneficial effects in reducing key components of chronic inflammatory responses.
Main Methods:
- Utilized the murine sponge model with subcutaneous and intraperitoneal polyether-polyurethane implants.
- Administered two doses of rolipram (0.2 or 2 mg/kg/day) orally for 7 days.
- Assessed angiogenesis via hemoglobin content and VEGF levels; inflammatory cell accumulation via MPO and NAG activities; cytokine production via TNF-alpha and MCP-1; and fibrosis via collagen and TGF-beta1 levels.
Main Results:
- Rolipram inhibited angiogenesis in subcutaneous implants by approximately 40% (hemoglobin and VEGF levels) but not in intraperitoneal implants.
- Neutrophil and macrophage accumulation (MPO and NAG activities) were attenuated in intraperitoneal implants but not subcutaneous ones.
- Rolipram decreased TNF-alpha and MCP-1 production in intraperitoneal implants, and reduced collagen and TGF-beta1 levels, indicating reduced fibrosis.
Conclusions:
- Rolipram demonstrates differential efficacy in modulating inflammatory processes based on tissue location.
- The study suggests potential for targeted therapeutic use of PDE4 inhibitors in specific inflammatory conditions.
- Rolipram may be useful for selectively targeting inflammatory angiogenesis.
