Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

IL-17RA Signaling Amplifies Antibody-Induced Arthritis

Objective: To investigate the role of IL-17RA signaling in the effector phase of inflammatory arthritis using the K/BxN serumtransfer model. Methods: Wild-type and Il17ra 2/2 mice were injected with serum isolated from arthritic K/BxN mice and their clinical score was recorded daily. Mice were also harvested on days 12 and 21 and ankles were analyzed for cytokine and chemokine mRNA expression by qPCR on day 12 and for bone and cartilage erosions by histology on day 21, respectively. The induction of cytokine and chemokine expression levels by IL-17A in synovial-like fibroblasts was also analyzed using qPCR. Results: Il17ra 2/2 mice were partially protected from clinical signs of arthritis and had markedly fewer cartilage and bone erosions. The expression of several pro-inflammatory mediators, including the chemokines KC/CXCL1, MIP-2/CXCL2, LIX/ CXCL5 MIP-1c/CCL9, MCP-3/CCL7, MIP-3a/CCL20, the cytokines IL-1b, IL-6, RANKL and the matrix metalloproteinases MMP2, MMP3, and MMP13 were decreased in the ankles of Il17ra 2/2 mice compared to wild-type mice. Many of these proinflammatory genes attenuated in the ankles of Il17ra 2/2 mice were shown to be directly induced by IL-17A in synovial fibroblasts in vitro. Conclusions: IL-17RA signaling plays a role as an amplifier of the effector phase of inflammatory arthritis. This effect is likel

Th17 Cytokines and the Gut Mucosal Barrier

Local immune responses serve to contain infections by pathogens to the gut while preventing pathogen dissemination to systemic sites. Several subsets of T cells in the gut (T-helper 17 cells, γδ T cells, natural killer (NK), and NK-T cells) contribute to the mucosal response to pathogens by secreting a subset of cytokines including interleukin (IL)-17A, IL-17F, IL-22, and IL-26. These cytokines induce the secretion of chemokines and antimicrobial proteins, thereby orchestrating the mucosal barrier against gastrointestinal pathogens. While the mucosal barrier prevents bacterial dissemination from the gut, it also promotes colonization by pathogens that are resistant to some of the inducible antimicrobial responses. In this review, we describe the contribution of Th17 cytokines to the gut mucosal barrier during bacterial infections

Summary of: Trigeminal nerve injuries in relation to the local anaesthesia in mandibular injections

Objective This study reports the signs and symptoms that are the features of trigeminal nerve injuries caused by local anaesthesia (LA). Methods Thirty-three patients with nerve injury following LA were assessed. All data were analysed using the SPSS statistical programme and Microsoft Excel. Results Lingual nerve injury (LNI; n = 16) and inferior alveolar nerve injury (IANI; n = 17) patients were studied. LNI were more likely to be permanent. Neuropathy was demonstrable in all patients with varying degrees of paraesthesia, dysaesthesia (in the form of burning pain) allodynia and hyperalgesia. All injuries were unilateral. A significantly greater proportion of LNI patients (75%) had received multiple injections, in comparison to IANI patients (41%) (p <0.05). Fifty percent of patients with LNI reported pain on injection. The presenting signs and symptoms of both LNI and IANI included pain. These symptoms of neuropathy were constant in 88% of the IANI group and in 44% of LNI patients. Functional difficulties were different between the LNI and IANI groups, a key difference being the presence of severely altered taste perception in nine patients with LA-induced LNI. Conclusions Chronic pain is often a symptom after local anaesthetic-induced nerve injury. Patients in the study population with lingual nerve injury were significantly more likely to have received multiple injections compared to those with IANI