The diagnostic value of cytokines for the discrimination of vertebral osteomyelitis and degenerative diseases of the spine.

Vertebral osteomyelitis (VO) is a primary infection of the endplates of the vertebral bodies with secondary infection of the adjacent intervertebral discs. Diagnosis is often delayed due to unspecific symptoms and a lack of specific infection markers. In this prospective study, we determined the suitability of 27 cytokines for the discrimination of VO and degenerative diseases of the spine and compared its diagnostic potential in relation to the C-reactive protein (CRP), which is widely used as a non-specific inflammation marker in clinical diagnostics. The patients included in this study underwent surgical stabilization of the lumbar and/or thoracic spine with removal of 1 or more affected intervertebral discs, as therapy for VO (n = 16) or for erosive osteochondrosis (EO, control group, n = 20). We evaluated the cytokine and CRP concentrations before (pre-OP = -20-0d where 0 means the day of surgery) and after surgery (post-OP) on days 3-5, 6-11, 40-56, and 63-142. Compared to the control patients pre-OP, a significantly higher elevation of the 4 cytokines IL-6, IL-8, IL-12 (p70), and VEGF as well as CRP were found in the VO patients, showing an area under the curve > 0.80 pre-OP. No significant differences were observed between VO patients with high and low virulent bacteria with respect to all 5 elevated biomarkers. This is the first prospective study in which a broad spectrum of 27 cytokines was analysed via multiplex assay using sera from patients with and without VO. Our results show that, in addition to CRP, 4 different cytokines were significantly altered in VO but not control patients. The results implicate that these candidate cytokines may be used in a multiplex assay for discrimination between VO and degenerative diseases of the spine.

Inflammatory Cytokine Levels in Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD).

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic ciliopathy that causes adult-onset progressive renal failure. Inflammation and the resulting fibrosis play a crucial role in the pathogenesis. In recent years, an increasing number of inflammatory markers such as MCP-1 and TNF-α, that are associated with the development and progression of ADPKD have been identified. The objective of this study was to identify and evaluate potential proinflammatory biomarkers in patients with ADPKD from the German AD(H)PKD registry. METHODS: In this exploratory pilot study, serum concentrations of IL-1ß, IL-2, IL-6, IL-8, IL-10, IL-13, IFN-γ, MCP-1 and TNF-α were measured by multiplex immunoassay in 233 adults patients with ADPKD from the German AD(H)PKD registry and compared to an age- and sex-matched healthy control group (n = 30). RESULTS: IL-6, IL-8, MCP-1, TNF-α and IFN-γ concentrations were significantly higher in patients with ADPKD than in healthy controls. In addition, sex influenced the concentrations of MCP-1 and TNF-α in the ADPKD and control groups (MCP-1 male =134.8 pg/l, female=75.11pg/l; p = 0.0055; TNF-α male=26.22pg/l, female=21.08 pg/l; p = 0.0038). CONCLUSION: In conclusion, patients with ADPKD have significantly higher levels of IL-6, IL-8, MCP-1, TNF-α and IFN-γ compared to healthy individuals. These findings underline that inflammation may play a crucial role in the pathogenesis of ADPKD and may be a potential target, both as biomarkers and for therapeutic interventions.

Oral D-Aspartate Treatment Improves Sperm Fertility in Both Young and Adult B6N Mice.

D-Aspartate (D-Asp) treatment improved the fertility of young male C57BL/6N mice in vivo revealing a direct role on capacitation, acrosome reaction, and fertility in vitro in young males only. We investigated whether the positive effect of D-Asp on fertility could be extended to adult males and evaluated the efficacy of a 2- or 4-week-treatment in vivo. Therefore, 20 mM sodium D-Asp was supplied in drinking water to males of different ages so that they were 9 or 16 weeks old at the end of the experiments. After sperm freezing, the in vitro fertilization (IVF) rate, the birth rate, hormone levels (luteinizing hormone (LH), epitestosterone, and testosterone), the sperm quality (morphology, abnormalities, motility, and velocity), the capacitation rate, and the acrosome reaction were investigated. Oral D-Asp treatment improves the fertilizing capability in mice regardless of the age of the animals. Importantly, a short D-Asp treatment of 2 weeks in young males elevates sperm parameters to the levels of untreated adult animals. In vivo, D-Asp treatment highly improves sperm quality but not sperm concentration. Therefore, D-Asp plays a beneficial role in mouse male fertility and may be highly relevant for cryorepositories to improve mouse sperm biobanking.

Of Mice and Men: The Coronavirus MHV and Mouse Models as a Translational Approach to Understand SARS-CoV-2.

The fatal acute respiratory coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since COVID-19 was declared a pandemic by the World Health Organization in March 2020, infection and mortality rates have been rising steadily worldwide. The lack of a vaccine, as well as preventive and therapeutic strategies, emphasize the need to develop new strategies to mitigate SARS-CoV-2 transmission and pathogenesis. Since mouse hepatitis virus (MHV), severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-CoV-2 share a common genus, lessons learnt from MHV and SARS-CoV could offer mechanistic insights into SARS-CoV-2. This review provides a comprehensive review of MHV in mice and SARS-CoV-2 in humans, thereby highlighting further translational avenues in the development of innovative strategies in controlling the detrimental course of SARS-CoV-2. Specifically, we have focused on various aspects, including host species, organotropism, transmission, clinical disease, pathogenesis, control and therapy, MHV as a model for SARS-CoV and SARS-CoV-2 as well as mouse models for infection with SARS-CoV and SARS-CoV-2. While MHV in mice and SARS-CoV-2 in humans share various similarities, there are also differences that need to be addressed when studying murine models. Translational approaches, such as humanized mouse models are pivotal in studying the clinical course and pathology observed in COVID-19 patients. Lessons from prior murine studies on coronavirus, coupled with novel murine models could offer new promising avenues for treatment of COVID-19.