Leonardo Punzi

Review; Authors: L. Punzi, C. Baggio, P. Galozzi, M. Lorenzin, G. Cozzi, A.C. Damasco, P. Sfriso, F. Oliviero, R. Ramonda

Review; Authors: L. Punzi, P. Galozzi, R. Luisetto, A. Scanu, R. Ramonda, F. Oliviero

We investigated the effects of bactericidal/permeability-increasing protein (BPI) alone or in combination with hyaluronic acid (HA) in two animal models: collagen-induced arthritis (CIA) and crystal-induced inflammation. In CIA, mice were intraperitoneally injected with PBS, HA, or BPI plus or minus HA, twice a week for 2 months, and then euthanized to collect paw and blood. Arthritis was assessed in ankle joints by clinical and histological evaluation. Pathogenic crystals were intraperitoneally injected in mice plus or minus BPI, or with a composition of BPI and HA. After sacrifice, total and differential leukocyte counts were determined. Cytokine levels were measured in serum and peritoneal fluids. In CIA mice, BPI improved clinical and histological outcomes (histological scores ≥2-fold), and downregulated inflammatory mediators (47–93%). In crystal-induced inflammation, BPI reduced leukocyte infiltration (total count: ≥60%; polymorphonuclear cells: ≥36%) and inhibited cytokine production (35–74%). In both models, when mice were co-treated with BPI and HA, the improvement of all parameters was greater than that observed after administration of the two substances alone. Results show that BPI attenuates CIA and inflammation in mice, and this effect is enhanced by HA co-administration. Combined use of BPI and HA represents an interesting perspective for new potential treatments in arthritis.

Autoinflammatory diseases (AIDs) are disorders characterised by recurrent inflammatory episodes in charge of different organs with no apparent involvement of autoantibodies or antigen-specific T lymphocytes. Few common clinical features have been identified among all monogenic AIDs (mAIDs), while the search for a common molecular pattern is still ongoing. The aim of this study was to increase knowledge on the inflammatory pathways in the development of mAIDs in order to identify possible predictive or diagnostic biomarkers for each disease and to develop future preventive and therapeutic strategies. Using protein array-based systems, we evaluated two signalling pathways known to be involved in inflammation and a wide range of inflammatory mediators (pro-inflammatory cytokines and chemokines) in a cohort of 23 patients affected by different mAIDs, as FMF, TRAPS, MKD, Blau syndrome (BS), and NLRP12D. Overall, we observed upregulation of multiple signalling pathway intermediates at protein levels in mAIDs patients’ PBMCs, compared with healthy controls, with significant differences also between patients. FMF, TRAPS, and BS presented also peculiar activations of inflammatory pathways that can distinguish them. MAPK pathway activation, however, seems to be a common feature. The serum level of cytokines and chemokines produced clear differences between patients with distinct diseases, which can help distinguish each autoinflammatory disease. The FMF cytokine production profile appears broader than that of TRAPS, which, in turn, has higher cytokine levels than BS. Our findings suggest an ongoing subclinical inflammation related to the abnormal and constitutive signalling pathways and define an elevated inflammatory cytokine signature. Moreover, the upregulation of Th17-related cytokines emphasises the important role for Th17 and/or Th17-like cells also in monogenic AIDs.

Background: Polydatin is a stilbenoid with important antioxidant, anti-inflammatory, and immunomodulating properties. The aim of this study was to assess the anti-inflammatory preventive effect of polydatin in the mouse model of acute arthritis induced by calcium pyrophosphate (CPP) crystals. Methods: Acute arthritis was induced by the injection of a suspension of sterile CPP crystals into the ankle joint of Balb/c mice. Animals were randomized to receive polydatin or colchicine (the control drug) according to a prophylactic and a therapeutic protocol. The primary outcome was the variation of ankle swelling obtained after crystal injection and treatment, while histological parameters such as leukocyte infiltration, IL-1ß and CXCL1 levels and tissue expression were considered as secondary outcomes. Results: Prophylactic treatment with PD significantly diminished ankle swelling after 48 h from crystal injection. Secondary outcomes such as leukocyte infiltration, necrosis, edema, and synovitis were also decreased. PD caused a reduction in circulating levels of IL-1ß and CXCL1, as well as their tissue expression. By contrast, the therapeutic administration of PD did not have any beneficial effect. Conclusions: PD can effectively prevent acute inflammatory response to crystals in the mouse model of CPP crystal-induced arthritis. These results suggest that this bioactive compound might be used in the prevention of crystal-induced acute attacks in humans.

The aim of this study was to evaluate the effect of an oral preparation containing a naturally occurring matrix of hydrolyzed collagen type II, chondroitin sulfate (CS), and hyaluronic acid (HA), and bioactive oligopeptides of natural hydrolyzed keratin (K) in patients affected by knee OA through the evaluation of synovial fluid (SF) and clinical changes before and after treatment. Thirty patients with knee OA and swollen joint were included in the study and submitted to arthrocentesis. Patients were randomized in two groups: 1) the treatment group (N.15) took a dietary supplement containing 120 mg HA, 240 mg CS and 300 mg K once a day for 4 weeks; 2) the control group (N.15) was only submitted to arthrocentesis. Patient symptoms were evaluated at the beginning and at the end of the study by the WOMAC self-assessment questionnaire, the Lequesne algofunctional index, and the VAS forms. SF changes were evaluated by measuring local inflammatory indices, cytokines IL-1β, IL-8, IL-6, IL-10 and GM-CSF. The group of patients treated with the oral supplement showed an improvement in the clinical indices WOMAC (p<0.01), Lequesne (p=0.014) and VAS pain (p<0.01). On the contrary, no significant changes were found in the control group. The SF collected from the treated group showed a reduction of IL-8 (p=0.015), IL-6 and IL-10 levels, while no changes in cytokines were observed in the control group. This pilot study suggests that an oral administration of a preparation containing a combination of HA, CS and K can improve some clinical parameters and affect cytokine concentrations in SF in patients with knee OA.

Gout is the most prevalent form of inflammatory arthritis, with a strong impact on individual health and healthcare systems. This article reviews clinical and experimental evidences about gout emerged throughout the 2019. Starting with an epidemiological analysis, the review explores new insights on genetic factors influencing the development of gout flare, pathogenetic mechanisms, risk factors for the disease and comorbidities. An overview on pharmacological therapies and recent knowledge on the impact of lifestyle and dietary habits are also included. Finally, the review contains a novel section on animal models, which reflects the renewed interest of researchers in the acute process triggered by monosodium urate crystals.