Background Inflammation in osteoarthritis (OA) has been characterized by infiltration of immune cells and secretion of cytokines into synovial tissues. Synovial macrophages production of IL-1beta and TNF-alfa is increased in response to lipopolysaccharide (LPS) suggesting a potential role of pathogen-associated molecular patterns (PAMPs) in OA development and/or evolution. Adrenergic activity have been associated with subchondral bone loss and increased osteoclast activity. Also, adrenergic activity is a main modulator of immune response to PAMPs in different settings. However,the relationship between activation of adrenergic and immune system with OA progression and treatment response remains still unknown.
Objectives To assess the adrenergic and immune activation in OA patients according to the presence of bacterial DNA (bDNA) fragments in blood before and after Chondroitin Sulfate/Glucosamine Hydrochloride (CS/GH) or Celecoxib (CE) treatment.
Methods Serum samples from patients participants in a 6-month controlled, double blind and randomized clinical trial comparing the analgesic efficacy of CS/GH and CE were analyzed to determine cytokines (IL-2, IL-4, IL-6, IL-10, IL-8, IL-1beta), catecholamines (noradrenaline, adrenaline and dopamine) and the presence of endotoxin or LPS and bDNA. Results are shown as mean±sd or median with ranges (Q25-Q75).
Results Samples from 100 OA patients (age: 62±8yr.; BMI: 31±6kg/m2 86 females; VAS: 73±15; WOMAC: 369±43) treated with CS/GH (50) or CE (50) were analyzed.There were no baseline significant differences between the two treatment groups regarding demographics,clinical and experimental variables. Thirty-four patients (17-CS/GH and 17-CE) showing bDNA in blood had significantly higher levels of noradrenaline compared with patients without bDNA (1993 [1354–3183] vs. 1324 [738–1899]; p=0.0002). After 6 months, both groups of treatment showed a similar reduction in VAS and WOMAC score (pain assessment) and serum adrenaline levels independent of presence or absence of bDNA (Table 1).Thirty-three patients showed bDNA presence at the end of the study (23 negative and 10 positive at baseline). Patients with bDNA at 6 months after treatment showed reduced serum noradrenaline levels compared with those observed in patients with bDNA at baseline (1993 [1354–3183] vs. 1561 [1174–2193]; p=0.0325). IL-8 was significantly reduced after 6 months of treatment only in patients without bDNA.There were no significant differences between baseline and 6 months samples in the other experimental variables.
Conclusions OA patients show bDNA fragments in blood associated to higher serum noradrenaline levels. Six month treatment with CS/GH or CE reduces significantly and in a similar fashion the pain intensity and adrenaline levels. IL-8 levels were reduced with the treatment except in patients with presence of bDNA fragments in blood. Systemic adrenergic and inflammatory activity in OA patients is influenced by the presence of PAMPs as bDNA in blood and this may be a factor to take into consideration to evaluate the severity, evolution and response to treatments.
Disclosure of Interest None declared