Post-traumatic arthritis (PTA) develops after an acute direct trauma to the joints. PTA causes about 12% of all osteoarthritis cases, and a history of physical trauma may also be found in patients with chronic inflammatory arthritis. Symptoms include swelling, synovial effusion, pain and sometimes intra-articular bleeding. Usually, PTA recoveries spontaneously, but the persistence of symptoms after 6 months may be considered pathological and so-called chronic PTA. A variety of molecular, mechanobiological and cellular events involved in the pathogenesis and the progression of PTA have been identified. The activation of inflammatory mechanisms during the PTA acute phase appears to play a critical role in the chronic disease onset. Human studies and experimental models have revealed that a series of inflammatory mediators are released in synovial fluid immediately after the joint trauma. These molecules have been proposed as markers of disease and as a potential target for the development of specific and preventative interventions. Currently, chronic PTA cannot be prevented, although a large number of agents have been tested in preclinical studies. Given the relevance of inflammatory reaction, anticytokines therapy, in particular the inhibition of interleukin 1 (IL-1), seems to be the most promising strategy. At the present time, intra-articular injection of IL-1 receptor antagonist is the only anticytokine approach that has been used in a human study of PTA. Despite the fact that knowledge in this area has increased in the past years, the identification of more specific disease markers and new therapeutic opportunities are needed.

Gout is the most common inflammatory arthropathy of metabolic origin and it is characterized by intense inflammation, the underlying mechanisms of which are unknown. The aim of this study was to evaluate the oxidative stress in human fibroblast-like synoviocytes (FLS) exposed to monosodium urate (MSU) crystals, which trigger an inflammatory process. Human FLS isolated from synovial tissue explants were stimulated with MSU crystals (75 μg/mL) for 24 h. Cellular viability was evaluated by crystal violet staining, apoptosis was assessed using Annexin V, and the cellular content of reactive oxygen species (ROS) and nitrogen species (RNS) (O2 -, H2O2, NO) was assessed with image-based cytometry and fluorometric methods. In order to determine protein oxidation levels, protein carbonyls were detected through oxyblot analysis, and cell ultrastructural changes were assessed by transmission electron microscopy. The viability of FLS exposed to MSU crystals decreased by 30 % (P < 0.05), while apoptosis increased by 42 % (P = 0.01). FLS stimulated with MSU crystals exhibited a 2.1-fold increase in H2O2 content and a 1.5-fold increase in O2 - and NO levels. Oxyblots revealed that the spots obtained from FLS protein lysates exposed to MSU crystals exhibited protein carbonyl immunoreactivity, which reflects the presence of oxidatively modified proteins. Concomitantly, MSU crystals triggered the induction of changes in the morphostructure of FLS, such as the thickening and discontinuity of the endoplasmic reticulum, and the formation of vacuoles and misfolded glycoproteins. Our results prove that MSU crystals induce the release of ROS and RNS in FLS, subsequently oxidizing proteins and altering the cellular oxidative state of the endoplasmic reticulum, which results in FLS apoptosis.

Imbalance in cytokine homeostasis plays an important part in the pathogenesis of chronic inflammatory diseases such as multiple sclerosis and rheumatoid arthritis. We demonstrated that T cells might exert a pathological effect through direct cellular contact with human monocytes/macrophages, inducing a massive up-regulation of the prototypical proinflammatory cytokines IL-1β and TNF. This mechanism that might be implicated in chronic inflammation is specifically inhibited by high-density lipoproteins (HDL). Like many other stimuli, besides proinflammatory cytokines, the contact-mediated activation of monocytes induces the production of cytokine inhibitors such as the secreted form of the IL-1 receptor antagonist (sIL-1Ra). The present study demonstrates that stimulated T cells generate microparticles (MP) that induce the production of TNF, IL-1β, and sIL-1Ra in human monocytes; the production of TNF and IL-1β but not that of sIL-1Ra is inhibited in the presence of HDL. The results were similar when monocytes were stimulated by whole membranes of T cells or soluble extracts of the latter. This suggests that MP carry similar monocyte-activating factors to cells from which they originate. Thus, by releasing MP, T cells might convey surface molecules similar to those involved in the activation of monocytes by cellular contact. By extension, MP might affect the activity of cells, which are usually not in direct contact with T cells at the inflammatory site. Furthermore, this study demonstrates that HDL exert an anti-inflammatory effect in nonseptic activation of human monocytes, not only by inhibiting the production of IL-1β and TNF but also, by leaving sIL-1Ra production unchanged.

Objectives To determine the most relevant parameters in synovial fluid (SF) during the various stages of acute gout. Methods SFs from 38 gouty patients were analysed for white blood cell (WBC) count, percentage of polymorphonuclear cells (PMNs) and levels of interleukin 1β (IL-1β), IL-6, IL-8, tumour necrosis factorα (TNFα) and transforming growth factor β1 (TGFβ1). Patients were divided into three groups according to the length of time since onset of the attack: phase I (0–48 h), phase II (days 3–4) and phase III (days 5–7). Results Levels of WBCs were similar in SFs from phases I and II, while phase III showed the lowest WBC count. Percentages of PMNs were raised in all SFs. None of the cytokines analysed differed between phases I and II except for TGFβ1, which was higher in phase II. IL-1β, IL-6 and TNFα were higher in group 1 than in group 3. Levels of all the cytokines assessed, with the exception of TGFβ1, were significantly lower in phase III than in phase II IL-1β, p<0.05; IL-6, p<0.01; IL-8, p<0.001; TNFα, p<0.05).TGFβ1 levels were highest in SFs from phase III. Conclusion Cytokine levels in SFs may change depending on the different stages of acute gout, highlighting the role of TGFβ1 in the resolution of gout.