Circulating levels of inflammatory cytokines and angiogenesis-related growth factors in patients with osteoarthritis after COVID-19

Abstract

BackgroundThe disease COVID-19, caused by SARS-CoV-2 infection, has a systemic effect and is associated with a number of pathophysiological mechanisms that mobilize a wide range of biomolecules. Cytokines and growth factors (GFs) are critical regulators of tissue damage or repair in osteoarthritis (OA) and are being recognized as key players in the pathogenesis of COVID-19. A clear understanding of the long-term consequences of SARS-CoV-2 infection, especially in patients with concomitant chronic diseases, is limited and needs to be elucidated. The study aimed to evaluate the degree of inflammation and levels of pro-angiogenic and hypoxic factors, as well as heat shock proteins HSP60 and HSP70 in plasma, of patients with OA after recovery from COVID-19.MethodsThe research involved patients of an orthopedic specialty clinic aged 39 to 80 diagnosed with knee OA. All examined patients were divided into three groups: the Control group included conditionally healthy donors, group OA included patients with knee OA mainly stage II or III and the group of OA and COVID-19 included patients with OA who had COVID-19. The plasma levels of pro-inflammatory molecules IL-1β, IL-6, TNF-α, NF-κB, angiogenic factors VEGF, FGF-2, PDGF, hypoxic factor HIF-1α and molecular chaperones HSP60 and HSP70 were measured by enzyme-linked immunosorbent assay.ResultsThe study showed that in both groups of patients, with OA and convalescent COVID-19, there was an increase in the plasma level of IL-1β and a decrease in TNF-α and NF-κB levels when compared to healthy controls. Systemic deregulation of the cytokine profile was accompanied by reduction in plasma levels of pro-angiogenic growth factors, most pronounced in cases of VEGF and PDGF. This analysis did not reveal any significant difference in the plasma level of HIF-1α. A decrease in the level of stress protein HSP60 in the blood of patients with OA, as well as those patients who have had SARS-CoV-2 infection, has been established.ConclusionThe results suggest the potential role pro-inflammatory cytokines and angiogenesis-related growth factors in pathogenesis of both joint pathologies and long-term systemic post-COVID-19 disorders.

Squamous papilloma involving the mandible: A case report and descriptive literature review

“…Prolonged inflammation can trigger the activation of local immune cells, leading to the release of proinflammatory cytokines, such as IL-1, TNF and IL-6, along with various growth factors. Among these factors are reactive oxygen species, reactive nitrogen species and interferon-γ ( 19 , 20 ). These cytokines in turn stimulate cell proliferation in the neighboring tissues, including the epithelial cells residing within the jawbone.…”

“…These cytokines in turn stimulate cell proliferation in the neighboring tissues, including the epithelial cells residing within the jawbone. This dysregulated cellular growth may cause the inception of papilloma formation ( 19 , 20 ). Close inter-cellular interplay may serve as another one of the four factors.…”

Inflammatory and Metabolic Signaling Interfaces of the Hypertrophic and Senescent Chondrocyte Phenotypes Associated with Osteoarthritis

“…In humans, in contrast to the variations of the aforementioned cytokines, changes in osteoarthritic plasma NF-kB and TNF-α levels may be moderate or even lower than in the healthy population [12]. A polyacrilamide gel-liquid chromatography-tandem mass spectrometry proteomics approach identified the presence of several factors and subunits of NF-kB in synovial fluid, such as NF-kB-repressing factor, NF-kB inhibitor-like protein 1, and NF-kB p100 subunit, which are normally found only in the intracellular space [8].…”

“…Another study comparing synovial protein patterns in early and advanced OA and controls found increased levels of albumin, fibrinogen, alpha1-microglobulin/bikunin precursor, α2-macroglobulin, haptoglobin, ceruloplasmin and other acute phase proteins, and decreased levels of cystatin A and aggrecan 1 [11]. Among the inflammatory mediators, levels of IL-1β and VEGF have been found to be higher in osteoarthritic than in normal sera, while IL-6 can reach 190-fold higher concentrations in OA synovial fluid than in serum [8,12]. CXCL1 can promote IL-6 synthesis in synovial fibroblasts [13].…”

Comparative proteomic profiling of the ovine and human PBMC inflammatory response

“…Moreover, during both systemic inflammatory responses and localized inflammatory reactions, cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, are released into the bloodstream, orchestrating a range of circulating immune cell activities, including activation, differentiation, and recruitment, while also triggering systemic responses, such as the stimulation of liver hepatocytes to synthesize and release acute phase proteins 35 – 37 . Consequently, the levels of peripheral blood cytokines have emerged as a crucial diagnostic and prognostic biomarker for both systemic and localized inflammatory responses, offering potential applications in the assessment of therapeutic efficacy and the optimization of treatment strategies in various diseases, including sepsis, asthma, atherosclerosis and osteoarthritis 38 – 40 .…”