IL-4-dependent regulation of TGF-alpha and TGF-beta1 expression in human eosinophils

TGFs play important roles in wound healing and carcinogenesis. We have previously demonstrated that eosinophils infiltrating into different pathologic processes elaborate TGF-alpha and TGF-beta1. Eosinophils infiltrating hamster cutaneous wounds were found to express TGFs sequentially. In this study, we examined the biologic mediators that may regulate the expression of TGF-alpha and -beta1 by eosinophils. Eosinophils were isolated from the peripheral blood of healthy donors and cultured in the absence or presence of IL-3, IL-4, and IL-5. Cells were analyzed by in situ hybridization and immunohistochemistry. Supernatants from these cultures were assayed for secreted TGF-alpha and TGF-beta1 using TGF-specific ELISAs. IL-3, IL-4, and IL-5 independently up-regulated TGF-beta1 mRNA and product expression by eosinophils in all donors. Interestingly, TGF-alpha production by eosinophils was up-regulated by IL-3 and IL-5 but was down-regulated by IL-4. Consistent with the ability of IL-4 to regulate eosinophil responses, IL-4 signaling molecules are present in human eosinophils. The observation that IL-4 can differentially regulate the expression of TGF-alpha and TGF-beta1 suggests that IL-4 may serve as a physiologic molecular switch of TGF expression by the infiltrating eosinophils in wound healing and carcinogenesis

Evidence-based review and assessment of botulinum neurotoxin for the treatment of adult spasticity in the upper motor neuron syndrome

Botulinum neurotoxin (BoNT) can be injected to achieve therapeutic benefit across a large range of clinical conditions. To assess the efficacy and safety of BoNT injections for the treatment of spasticity associated with the upper motor neuron syndrome (UMNS), an expert panel reviewed evidence from the published literature. Data sources included English-language studies identified via MEDLINE, EMBASE, CINAHL, Current Contents, and the Cochrane Central Register of Controlled Trials. Evidence tables generated in the 2008 Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (AAN) review of the use of BoNT for autonomic disorders were also reviewed and updated. The panel evaluated evidence at several levels, supporting BoNT as a class, the serotypes BoNT-A and BoNT-B, as well as the four individual commercially available formulations: abobotulinumtoxinA (A/Abo), onabotulinumtoxinA (A/Ona), incobotulinumtoxinA (A/Inco), and rimabotulinumtoxinB (B/Rima). The panel ultimately made recommendations on the effectiveness of BoNT for the management of spasticity, based upon the strength of clinical evidence and following the AAN classification scale. While the prior report by the AAN provided recommendations for the use of BoNT as a class of drug, this report provides more detail and includes recommendations for the individual formulations. For the treatment of upper limb spasticity, the evidence supported a Level A recommendation for BoNT-A, A/Abo, and A/Ona, with a Level B recommendation for A/Inco; there was insufficient evidence to support a recommendation for B/Rima. For lower limb spasticity, there was sufficient clinical evidence to support a Level A recommendation for A/Ona individually and BoNT-A in aggregate; the clinical evidence for A/Abo supported a Level C recommendation; and there was insufficient information to recommend A/Inco and B/Rima (Level U). There is a need for further comparative effectiveness studies of the available BoNT formulations for the management of spasticity. \ua9 2013 Elsevier Ltd