Systemic Dermatitis Model Mice Exhibit Atrophy of Visceral Adipose Tissue and Increase Stromal Cells via Skin-Derived Inflammatory Cytokines.

: Adipose tissue (AT) is the largest endocrine organ, producing bioactive products called adipocytokines, which regulate several metabolic pathways, especially in inflammatory conditions. On the other hand, there is evidence that chronic inflammatory skin disease is closely associated with vascular sclerotic changes, cardiomegaly, and severe systemic amyloidosis in multiple organs. In psoriasis, a common chronic intractable inflammatory skin disease, several studies have shown that adipokine levels are associated with disease severity. Chronic skin disease is also associated with metabolic syndrome, including abnormal tissue remodeling; however, the mechanism is still unclear. We addressed this problem using keratin 14-specific caspase-1 overexpressing transgenic (KCASP1Tg) mice with severe erosive dermatitis from 8 weeks of age, followed by re-epithelization. The whole body and gonadal white AT (GWAT) weights were decreased. Each adipocyte was large in number, small in size and irregularly shaped; abundant inflammatory cells, including activated CD4+ or CD8+ T cells and toll-like receptor 4/CD11b-positive activated monocytes, infiltrated into the GWAT. We assumed that inflammatory cytokine production in skin lesions was the key factor for this lymphocyte/monocyte activation and AT dysregulation. We tested our hypothesis that the AT in a mouse dermatitis model shows an impaired thermogenesis ability due to systemic inflammation. After exposure to 4 °C, the mRNA expression of the thermogenic gene uncoupling protein 1 in adipocytes was elevated; however, the body temperature of the KCASP1Tg mice decreased rapidly, revealing an impaired thermogenesis ability of the AT due to atrophy. Tumor necrosis factor (TNF)-α, IL-1ß and interferon (INF)-γ levels were significantly increased in KCASP1Tg mouse ear skin lesions. To investigate the direct effects of these cytokines, BL/6 wild mice were administered intraperitoneal TNF-α, IL-1ß and INF-γ injections, which resulted in small adipocytes with abundant stromal cell infiltration, suggesting those cytokines have a synergistic effect on adipocytes. The systemic dermatitis model mice showed atrophy of AT and increased stromal cells. These findings were reproducible by the intraperitoneal administration of inflammatory cytokines whose production was increased in inflamed skin lesions.

Strategies to prevent hypertrophic scar formation: a review of therapeutic interventions based on molecular evidence.

Once scar tissues mature, it is impossible for the surrounding tissue to regenerate normal dermal tissue. Therefore, it is essential to understand the fundamental mechanisms and establish effective strategies to inhibit aberrant scar formation. Hypertrophic scar formation is considered a result of the imbalance between extracellular matrix synthesis and degradation during wound healing. However, the underlying mechanisms of hypertrophic scar development are poorly understood. The purpose of this review was to outline the management in the early stage after wound healing to prevent hypertrophic scar formation, focusing on strategies excluding therapeutic agents of internal use. Treatment aimed at molecular targets, including cytokines, will be future options to prevent and treat hypertrophic scars. More basic studies and clinical trials, including combination therapy, are required to investigate the mechanisms and prevent hypertrophic scar formation.

Lymphovenous anastomosis for the treatment of persistent congenital chylothorax in a low-birth-weight infant: A case report.

RATIONALE: Chylothorax remains a poorly understood phenomenon, and no optimal treatment or guidelines have been established. This is the first report of treating congenital chylothorax and lymphedema in a low-birth-weight infant by lymphovenous anastomosis (LVA). PATIENT CONCERNS: We report a case of successful LVA for persistent congenital chylothorax and lymphedema resistant to other conservative therapies. DIAGNOSIS: The diagnosis of chylothorax was confirmed by the predominance of lymphocytes in the pleural fluid draining from the chest tube. In addition, the infant developed oliguria and generalized lymphedema. INTERVENTIONS: LVA under local anesthesia combined with light sedation was performed at his medial thighs and left upper arm. OUTCOMES: Although his subcutaneous edema markedly improved, the decrease in chest tube drainage was gradual. No additional treatment was required. LESSONS: LVA is of considerable value as a surgical treatment option in the setting of persistent congenital chylothorax and lymphedema, because LVA is a less invasive procedure.