Interleukin-12p40 Modulates Human Metapneumovirus-Induced Pulmonary Disease in an Acute Mouse Model of Infection

The mechanisms that regulate the host immune response induced by human metapneumovirus (hMPV), a newly-recognized member of the Paramyxoviridae family, are largely unknown. Cytokines play an important role in modulating inflammatory responses during viral infections. IL-12p40, a known important mediator in limiting lung inflammation, is induced by hMPV and its production is sustained after the resolution phase of infection suggesting that this cytokine plays a role in the immune response against hMPV. In this work, we demonstrated that in mice deficient in IL-12p40, hMPV infection induced an exacerbated pulmonary inflammatory response and mucus production, altered cytokine response, and decreased lung function. However, hMPV infection in these mice does not have an effect on viral replication. These results identify an important regulatory role of IL-12p40 in hMPV infection

Validation of the short version of the Van Lieshout test in an italian population with cervical spinal cord injuries: a cross-sectional study

Study design: Psychometric study. Objective: To validate the Italian version of the Van Lieshout Test Short Version (VLT-SV) with a spinal cord injury population. Setting: Three Italian spinal units. Methods: The Italian version of the VLT-SV (VLT-SV-IT) was administered to a sample of people with cervical spinal cord injuries (C-SCI) and the test–retest was performed. Reliability was assessed using Cronbach’s alpha for internal consistency and the intraclass correlation coefficient for repeatability assessment (test–retest). Pearson’s correlation coefficient was calculated for concurrent validity with the Italian version of the Jebsen–Taylor Hand Function Test (JTHFT) and for construct validity with the Italian version of the Spinal Cord Injury Independence Measure (SCIM III). Results: The VLT-SV-IT was administered to 61 individuals and all psychometric properties were significant: Cronbach’s alpha was 0.95 (left hand and right hand) and the intraclass correlation coefficient for test–retest reliability was 0.90 for the right hand, the left hand, and the total score. Pearson’s correlation coefficient of the VLT-SV-IT with the JTHFT was significant, while the correlation with SCIM III was not. The obtained values are considered acceptable and consistent with international guidelines. Conclusions: The VLT-SV-IT was shown to be a reliable and valid assessment tool for measuring hand function in the Italian population with C-SCI. This result suggests that it could be used as a starting point for hand therapy and to assist in clinical decision-making regarding treatment policy

Mast cells modulate the pathogenesis of elastase-induced abdominal aortic aneurysms in mice

Abdominal aortic aneurysm (AAA), an inflammatory disease, involves leukocyte recruitment, immune responses, inflammatory cytokine production, vascular remodeling, neovascularization, and vascular cell apoptosis, all of which contribute to aortic dilatation. This study demonstrates that mast cells, key participants in human allergic immunity, participate in AAA pathogenesis in mice. Mast cells were found to accumulate in murine AAA lesions. Mast cell–deficient KitW-sh/KitW-sh mice failed to develop AAA elicited by elastase perfusion or periaortic chemical injury. KitW-sh/KitW-sh mice had reduced aortic expansion and internal elastic lamina degradation; decreased numbers of macrophages, CD3+ T lymphocytes, SMCs, apoptotic cells, and CD31+ microvessels; and decreased levels of aortic tissue IL-6 and IFN-γ. Activation of mast cells in WT mice via C48/80 injection resulted in enhanced AAA growth while mast cell stabilization with disodium cromoglycate diminished AAA formation. Mechanistic studies demonstrated that mast cells participated in angiogenesis, aortic SMC apoptosis, and matrix-degrading protease expression. Reconstitution of KitW-sh/KitW-sh mice with bone marrow–derived mast cells from WT or TNF-α–/– mice, but not from IL-6–/– or IFN-γ–/– mice, caused susceptibility to AAA formation to be regained. These results demonstrate that mast cells participate in AAA pathogenesis in mice by releasing proinflammatory cytokines IL-6 and IFN-γ, which may induce aortic SMC apoptosis, matrix-degrading protease expression, and vascular wall remodeling, important hallmarks of arterial aneurysms