Leukocyte antigen HLA-B27 influenced serum IL-6 concentrations. From a clinical point of view, in the axial forms (pure or mixed) not associated with HLA-B27, IL-6 concentrations were higher than in these clinical forms where the HLA-B27 was present. Serum levels of IL-6 and TNF-α had no impact on the inflammatory activity of the disease measured by joint swelling, by the number of entheses affected or by the severity of psoriasis. Neither did they influence fatigue or variables related to cardiovascular comorbidity, except for the association of serum TNF-α levels with subclinical renal damage.
Regarding the association between serum levels of IL-6 and the presence of HLA-B27, indirectly, these results agree with a previous study, where the relationship between the IL-6 polymorphism (-174 G / C) and the presence of HLA-B27, in it, the G allele of the polymorphism, related to an increase in transcriptional activity and secondarily with higher levels of IL-6, was significantly associated with negative HLA-B27 [5, 17].
Although we found a strong correlation between IL-6 concentrations and CRP, (related to hepatic release of IL-6-induced acute phase reactants) we found no relationship with other clinical parameters of inflammation . In a Swedish study, IL-6 levels were related to SJC, using the Moll and Wright criteria, this study obtained higher concentrations of IL-6 among patients with joint involvement associated with rheumatoid factor .
However, the increased expression of IL-6 in the synovium of patients with PsA could have demonstrated that IL-6 inhibition could be useful in the treatment of PsA. At the moment the results have not been categorical, in most of the patients treated with Tocilizumab, the inhibition of IL-6 was correlated with a decrease in of CRP levels, although a decrease in the clinical activity of the patients did not always occur [20, 21]. Recently, in a randomized study, IL-6 blockade with clazakizumab showed efficacy in joint manifestations, measured by both the ACR20 response (at the 100 mg dose; 52.4 vs 29.3; p < 0.039) as by SJC and / or TJC. There was also a response in enthesitis and dactylitis. There was no improvement in skin parameters . In our study, as in other studies, there was no relationship between IL-6 levels and skin involvement measured by PASI .
Neither did we find a correlation between the serum TNF α level and SJC, TJC, VAS, enthesitis, dactylitis, CRP or ESR. In a recent study, Caso et al. found similar results . In patients with spondylitis, there was also no relationship between serum TNF-α and ESR or CRP . In our study, serum TNF α concentrations were higher in patients who were receiving TNF α inhibitors. This finding may be due to the fact that TNF-α blockade causes secondary hyperproduction of TNF-α. Furthermore, patients achieving a MDA had higher concentrations of TNF-α. This result would be secondary to the higher proportion of treatment with TNF-α inhibitors in the group of patients who achieved a MDA. Excluding patients who were treated with TNF-α inhibitors, we also found no correlation between TNF-α and activity parameters or PASI. In previous studies, although patients with psoriasis had higher concentrations of TNF-α than in controls, these also did not correlate with the severity of psoriasis .
In our study, the intensity of fatigue was not correlated with the concentrations of IL-6 or TNF-α. The multifactorial etiology of fatigue may justify this result. Indeed, although it has been documented in animal models that IL-6 concentrations are related to muscle weakness and that blocking IL-6 and TNF α in patients with PsA produces a slight improvement in fatigue. However, the intensity of fatigue may be due to other causes, such as emotional disturbances, not directly linked to inflammation [22, 24–27].
Adipose tissue is metabolically active and produces IL-6 or TNF-α that can influence the inflammatory activity of the disease [28. On the other hand, the involvement of IL-6 in vascular morbidity associated with obesity is controversial, although previous studies it has been correlated with the presence of atherosclerosis in the coronary arteries. However, the administration of IL-6 improves the use of insulin and the oxidation of fatty acids, in addition treatment with IL-6 inhibitors increases cholesterol concentrations [6, 29–31].
In our study, we did not find an association between serum IL-6 levels and the waist / hip ratio or the other parameters associated with obesity. These results coincide with those obtained with TNF α, except for the association with MA. MA is a marker of generalized vascular dysfunction that behaves as a cardiovascular risk factor . Currently, there are no references to the presence of MA in patients with PsA, however, there are studies that link inflammation with MA. In patients with rheumatoid arthritis (RA), MA was more frequent than in healthy subjects, and it was also associated with inflammatory parameters such as DAS28, ESR, and ultrasensitive CRP . In these patients, the severity of the MA was greater according to the degree of inflammation measured by the number of joints affected. In our study, however, there was no correlation with clinical disease activity, CRP, or ESR (Data not shown). In other studies with RA patients, there was no relationship between MA and TNF-α or IL-6 levels . In patients with diabetes, the presence of soluble TNF-α and IL-6 receptors has been associated with MA. The TNF-α / IL-6 pathway would be activated in up to 40% of patients with MA, with which these cytokines could be used as biomarkers of early kidney damage . Inflammation can cause kidney damage through different mechanisms. TNF-α acts on Th1 lymphocytes, increasing the adhesion molecules of the renal vascular endothelium and promoting the migration of lymphocytes and leukocytes that cause endothelial dysfunction and associated kidney damage .
One of the limitations of the study is its cross-sectional nature, longitudinal studies would better catalog patients with sustained elevations of IL-6 and TNF-α and their consequences on activity, clinical form and comorbidities.