Short-term Obesity Worsens Heart Inflammation and Disrupts Mitochondrial Biogenesis and Function in an Experimental Model of Endotoxemia.

Cardiomyopathy is a well-known complication of sepsis that may deteriorate when accompanied by obesity. To test this hypothesis we fed C57black/6 male mice for 6 week with a high fat diet (60% energy) and submitted them to endotoxemic shock using E. coli LPS (10 mg/kg). Inflammatory markers (cytokines and adhesion molecules) were determined in plasma and heart tissue, as well as heart mitochondrial biogenesis and function. Obesity markedly shortened the survival rate of mouse after LPS injection and induced a persistent systemic inflammation since TNFα, IL-1ß, IL-6 and resistin plasma levels were higher 24 h after LPS injection. Heart tissue inflammation was significantly higher in obese mice, as detected by elevated mRNA expression of pro-inflammatory cytokines (IL-1ß, IL-6 and TNFα). Obese animals presented reduced maximum respiratory rate after LPS injection, however fatty acid oxidation increased in both groups. LPS decreased mitochondrial DNA content and mitochondria biogenesis factors, such as PGC1α and PGC1ß, in both groups, while NRF1 expression was significantly stimulated in obese mice hearts. Mitochondrial fusion/fission balance was only altered by obesity, with no influence of endotoxemia. Obesity accelerated endotoxemia death rate due to higher systemic inflammation and decreased heart mitochondrial respiratory capacity.

Bone Marrow Cells Transplant in Septic Mice Modulates Systemic Inflammatory Response via Cell-Cell Contact.

Sepsis is a dynamic disease, displaying an inflammatory profile that varies over time and for each organ. Controlling the inflammatory response based in targeting a single molecule has been proved useless. We hypothesized that treatment with bone marrow-derived mononuclear cells (BMDMCs) may be more efficient to modulate the systemic inflammatory response to infection. Adult male Balb/c mice were subjected to cecal ligation and puncture (CLP) or endotoxemia model of experimental sepsis. BMDMCs were separated under Ficoll gradient and injected intravenously 1 h after the procedures. Cytokines concentration was quantified in plasma, lungs, heart, and gut. Spleens, lymph nodes, and thymus were used for lymphocytes isolation and cell death assessment. All measurements were performed 2 h after BMDMCs injection. RAW264.7 macrophages and BMDMCs were cocultivated in vitro to investigate the mechanisms involved. Our data showed that an early single intravenous injection of BMDMCs in animals submitted to the murine model of endotoxemia led to the improvement of survival rate; BMDMCs persistency in lung, liver, and spleen after 24 h; decreased necrosis and apoptosis of mononuclear cells; lower TNF-α, but increased IL-10 concentration in plasma; and tissue-specific cytokine profile. In vitro experiments demonstrated that IL-6, IL-10, and nitric oxide production depends on direct contact of BMDMCs to macrophages and that TNF-α production is negatively regulated by PGE2. BMDMCs are efficient in protecting animals from endotoxemia and sepsis, reducing systemic inflammation as well as specifically modulating tissue inflammation, producing the necessary immune regulation to re-equilibrate the inflammatory response.

Low level laser therapy reduces acute lung inflammation without impairing lung function.

Acute lung injury is a condition characterized by exacerbate inflammatory reaction in distal airways and lung dysfunction. Here we investigate the treatment of acute lung injury (ALI) by low level laser therapy (LLLT), an effective therapy used for the treatment of patients with inflammatory disorders or traumatic injuries, due to its ability to reduce inflammation and promote tissue regeneration. However, studies in internal viscera remains unclear. C57BL/6 mice were treated with intratracheal lipopolysaccharide (LPS) (5 mg/kg) or phosphate buffer saline (PBS). Six hours after instillation, two groups were irradiated with laser at 660 nm and radiant exposure of 10 J/cm2 . Intratracheal LPS inoculation induced a marked increase in the number of inflammatory cells in perivascular and alveolar spaces. There was also an increase in the expression and secretion of cytokines (TNF-α, IL-1ß, IL-6,) and chemokine (MCP-1). The LLLT application induced a significant decrease in both inflammatory cells influx and inflammatory mediators secretion. These effects did not affect lung mechanical properties, since no change was observed in tissue resistance or elastance. In conclusion LLLT is able to reduce inflammatory reaction in lungs exposed to LPS without affecting the pulmonary function and recovery.

Effect of laser phototherapy on wound healing following cerebral ischemia by cryogenic injury.

Laser phototherapy emerges as an alternative or auxiliary therapy for acute ischemic stroke, traumatic brain injury, degenerative brain disease, spinal cord injury, and peripheral nerve regeneration, but its effects are still controversial. We have previously found that laser phototherapy immunomodulates the response to focal brain damage. Following direct cortical cryogenic injury the effects of laser phototherapy on inflammation and repair was assessed after cryogenic injury (CI) to the central nervous system (CNS) of rats. The laser phototherapy was carried out with a 780 nm AlGaAs diode laser. The irradiation parameters were: power of 40 mW, beam area of 0.04 cm(2), energy density of 3 J/cm(2) (3s) in two points (0.12 J per point). Two irradiations were performed at 3 h-intervals, in contact mode. Rats (20 non-irradiated - controls and 20 irradiated) were used. The wound healing in the CNS was followed in 6 h, 1, 7 and 14 days after the last irradiation. The size of the lesions, the neuron cell viability percentages and the amount of positive GFAP labeling were statistically compared by ANOVA complemented by Tukey's test (p<0.05). The distribution of lymphocytes, leukocytes and macrophages were also analyzed. CI created focal lesions in the cortex represented by necrosis, edema, hemorrhage and inflammatory infiltrate. The most striking findings were: lased lesions showed smaller tissue loss than control lesions in 6 h. During the first 24 h the amount of viable neurons was significantly higher in the lased group. There was a remarkable increase in the amount of GFAP in the control group by 14 days. Moreover, the lesions of irradiated animals had fewer leukocytes and lymphocytes in the first 24 h than controls. Considering the experimental conditions of this study it was concluded that laser phototherapy exerts its effect in wound healing following CI by controlling the brain damage, preventing neuron death and severe astrogliosis that could indicate the possibility of a better clinical outcome.