IL-22 and IL-22 binding protein (IL-22BP) regulate fibrosis and cirrhosis in hepatitis C virus and schistosome infections.

UNLABELLED: Interleukin (IL)-22 acts on epithelia, hepatocytes, and pancreatic cells and stimulates innate immunity, tissue protection, and repair. IL-22 may also cause inflammation and abnormal cell proliferation. The binding of IL-22 to its receptor is competed by IL-22 binding protein (IL-22BP), which may limit the deleterious effects of IL-22. The role of IL-22 and IL-22BP in chronic liver diseases is unknown. We addressed this question in individuals chronically infected with schistosomes or hepatitis C virus (HCV). We first demonstrate that schistosome eggs stimulate production of IL-22 transcripts and inhibit accumulation of IL22-BP transcripts in schistosome-infected mice, and that schistosome eggs selectively stimulate production of IL-22 in cultures of blood leukocytes from individuals chronically infected with Schistosoma japonicum. High IL-22 levels in cultures correlated with protection against hepatic fibrosis and portal hypertension. To test further the implication of IL-22/IL-22BP in hepatic disease, we analyzed common genetic variants of IL22RA2, which encodes IL-22BP, and found that the genotypes, AA, GG of rs6570136 (P = 0.003; odds ratio [OR] = 2), and CC, TT of rs2064501 (P = 0.01; OR = 2), were associated with severe fibrosis in Chinese infected with S. japonicum. We confirmed this result in Sudanese (rs6570136 GG [P = 0.0007; OR = 8.2], rs2064501 TT [P = 0.02; OR = 3.1]), and Brazilians (rs6570136 GG [P = 0.003; OR = 26], rs2064501 TC, TT (P = 0.03; OR = 11]) infected with S. mansoni. The aggravating genotypes were associated with high IL22RA2 transcripts levels. Furthermore, these same variants were also associated with HCV-induced fibrosis and cirrhosis (rs6570136 GG, GA [P = 0.007; OR = 1.7], rs2064501 TT, TC (P = 0.004; OR = 2.4]). CONCLUSIONS: These results provide strong evidence that IL-22 protects against and IL-22BP aggravates liver fibrosis and cirrhosis in humans with chronic liver infections. Thus, pharmacological modulation of IL-22 BP may be an effective strategy to limit cirrhosis.

Scar prevention using Laser-Assisted Skin Healing (LASH) in plastic surgery.

BACKGROUND: The use of lasers has been proposed for scar revision. A recent pilot clinical study demonstrated that lasers could also be used immediately after surgery to reduce the appearance of scars. The LASH (Laser-Assisted Skin Healing) technique induces a temperature elevation in the skin which modifies the wound-healing process. We report a prospective comparative clinical trial aimed at evaluating an 810-nm diode-laser system to accelerate and improve the healing process in surgical scars immediately after skin closure. METHODS: Twenty-nine women and 1 man (mean age = 41.4 years; Fitzpatrick skin types I-IV) were included to evaluate the safety and performance of the laser system. The laser dose (or fluence in J/cm(2)) was selected as a function of phototype and skin thickness. Each surgical incision (e.g., abdominoplasty) was divided into two parts. An 8-cm segment was treated with the laser immediately after skin closure. A separate 8-cm segment was left untreated as a control. Clinical evaluations (overall appearance ratings, comparative scar scale) of all scars were conducted at 10 days, 3 months, and 12 months by both surgeon and patients. Profilometry analysis from silicone replicas of the skin was done at 12 months. Wilcoxon signed-rank test analyses were performed. RESULTS: Twenty-two patients were treated using a high dose (80-130 J/cm(2)) and 8 patients with a low dose (<80 J/cm(2)). At 12 months in the high-dose group, both surgeon and patients reported an improvement rate of the laser-treated segment over the control area of 72.73 and 59.10%, respectively. For these patients, profilometry results showed a decrease in scar height of 38.1% (p = 0.027) at 12 months for the laser-treated segment versus control. Three patients treated with higher doses (>115 J/cm(2)) experienced superficial burns on the laser-treated segment, which resolved in about 5-7 days. For the eight patients treated at low dosage (<80 J/cm(2)), there was no significant difference in the treated segment versus the control segment. No side effects were observed. CONCLUSION: This prospective comparative trial demonstrates that an 810-nm diode laser treatment, performed immediately after surgery, can improve the appearance of a surgical scar. The dose plays a great role in scar improvement and must be well controlled. There is interest in LASH for hypertrophic scar revision. LASH can be used to prevent and reduce scars in plastic surgery.