Interleukin-1α and interleukin-6 serum levels
IL-1α was statistically significant higher among psoriatic cases than in control group (3.85±2.0 vs. 0.80±0.25 µg/ml) (Fig. 2c), and was correlated positively with duration of disease (r=0.33, P=0.006), PASI score (r=0.87, P=0.001) and MPV (r=0.75, P=0.001) (Table 3).
Parallel to IL-1 α, IL-6 had significant higher values among psoriatic cases than their matched controls (48.80±13.59 vs. 8.91±0.98 µg/ml) (Fig. 2d), and showed significant positive correlation with duration of disease (r=0.28, P=0.02), PASI score (r=0.81, P=0.001), and MPV (r=0.75, P=0.001) among psoriatic cases (Table 3).
Carotid intima media thickness of studied participants
The mean value of CIMT were significantly (P=0.001) higher in psoriatic patients than controls (0.91±0.20 vs. 0.65±0.13 mm) (Fig. 2b). In psoriatic patient group, this elevated CIMT was significantly correlated with; age of psoriatic patients (r=0.66, P=0.01), duration of illness (r=0.65, P<0.05), PASI score (r=0.67, P<0.05) and MPV (r=0.71, P<0.001), but not with age of psoriasis onset (Table 3).
According to estimated CIMT values; psoriatic patients (70 cases) were subdivided into atherosclerotic (44 psoriatic patients who have CIMT>0.8 mm) and nonatherosclerotic (26 cases having CIMT≤0.08 mm) psoriatic patients. compared with nonatherosclerotic, atherosclerotic psoriatic patients were significantly older (43.50±6.53 vs. 39.41±10.06 years), and had significantly longer disease duration (8.77±3.18 vs. 7.08±3.46 years) and severe form of psoriasis (elevated PASI score) (14.29±5.50 vs. 10.41±2.53). In addition, significantly higher values of MPV (10.08 ±1.07 vs. 8.92±0.78 fl), IL-1α (4.60±2.16 vs. 2.58±0.61 µg/ml), and IL-6 (54.32±12.88 vs. 39.46±8.95 µg/ml) were demonstrated among atherosclerotic psoriatic patients than those without atherosclerotic changes (Table 4).
Receiver operating characteristic curve analysis and cutoff point of mean platelet volume, interleukin-1α, and interleukin-6 for early diagnosis of atherosclerosis in psoriasis patients
Receiver operating characteristic curve analysis for MPV, IL-1α and IL-6 as early predictors of atherosclerosis among psoriasis patients demonstrated that MPV showed the most accurate (80.0%) and highest sensitive (90.9%), followed by IL-1α (77.1, 86.4%) then IL-6 (68.6, 72.7%) respectively. The specificity of the three markers was similar (61.5% for all). The cutoff point for MPV was 8.95 fl, and that for IL-1 and IL-6 were 2.55 and 43.3 µg/ml, respectively (Fig. 3).
To best of our knowledge, this study is the first one to verify the predictive role of the MPV in early diagnosis of atherosclerosis in psoriatic patients. Modern advances in clinical research, laboratory procedures have opened the door for a better understanding of platelets role in inflammation, thrombosis, immunity and angiogenesis 25. Therefore, investigation of platelet activation in patients with psoriasis may help in the measuring of both psoriasis activity and atherosclerotic risk.
In this study, the MPV in psoriatic patients was significantly higher than that of control group, and was positively correlated with PASI score, denoting that patients with psoriasis have increased platelet activation and those with severe form of psoriasis are associated with more increase in this activity, which suggests an essential role of systemic platelet activation in the course of psoriasis development. Furthermore, MPV is associated with psoriasis severity.
We have observed also that MPV of at least 8.85 fl is a good sensitive test (accuracy=80.0%; sensitivity=90.9%) for predicting atherosclerosis in psoriatic patients. In line with our findings, Canpolat et al.26 and Kim et al.14, reported that mean MPV in patients with psoriasis was significantly elevated compared with controls, and significantly correlated with severity of psoriasis. Although Saleh et al.27 revealed nonsignificant increase in MPV in psoriatic patients than controls, and denied its correlation with disease severity. Differences in study population by Saleh et al.27 (two men and seven women had mild psoriasis, whereas 11 men and five women had moderate/severe psoriasis) and in MPV estimation method could explain its disagreement to our study findings. Saleh et al. 27 examined MPV in their study by Coulter LH-750 analyzer which uses impedance method for size calculation while detecting CD62 by flow cytometry. In our study, we used Sysmex XN-1000 with an improved platelet analysis, it uses a platelet-specific fluorescent dye that is similar to detecting CD62 in Saleh et al.27, who reported a negative correlation of MPV with CD62 (−0.16). Moreover, psoriasis has periods of exacerbation and remission with variable PASI score 28.
In accordance with Canpolat et al.26, we noticed significant positive correlation between MPV and duration of psoriasis. In addition, we observed significant positive association between MPV with patients’ age and age of onset of psoriasis.
In view of these findings, we can suggest that platelet activation, evaluated by high MPV, may have a significant role not only in psoriasis development but also in its outcome, supporting the previous hypothesis concerning the active role of platelets in aetiopathogenesis of psoriasis 10.
In the same context we measured CIMT, the actual sonographic marker of early atherosclerotic alteration 18, to detect early atherosclerotic changes in our studied participants. Ultrasonography data of this study revealed that psoriasis is an independent risk factor for subclinical atherosclerosis, as psoriatic patients, who have no obvious clinical atherosclerosis or atherosclerotic risk, had significant high CIMT. In addition, 44/70 (63%) of psoriasis patients had atheroscelotic CIMT measurements, had longer disease duration (8.77±3.18 vs. 7.08±3.46 years) and severe form of psoriasis (elevated PASI score: 14.29±5.50 vs. 10.41±2.53) compared with 26/70 psoriasis patients. This observation was supported by previous studies in which the authors reported high prevalence of subclinical atherosclerosis in psoriatic patients 18,29,30.
Furthermore, CIMT of our psoriatic patients was not only positively correlated with severity of psoriasis, but also with its duration of and age of those patients. This indicates that elderly psoriatic patients with long duration and severe form of psoriasis are more prone to develop atherosclerosis than young patients with short duration, and less severe form of the disease. This may approve the assumption that one of the reasons of increased risk and early development of atherosclerosis in patients with psoriasis is a common inflammatory pathway of both diseases 28.
Proposing the role of platelet activity in pathogenesis of atherosclerosis 10, our result showed significant positive correlation between MPV and CIMT in studied psoriatic patients. In addition to the previous mentioned significant higher MPV in the same psoriatic patients than controls, we suggested that platelet activation may form a link between psoriasis and subclinical atherosclerosis. However, Saleh et al.27 proved this hypothesis by measuring another platelet activity marker (CD62) using flow cytometry.
In the current work, significant increase in CIMT mean value in psoriatic patients than controls, and its significant positive correlations with age of psoriatic patients, duration of psoriasis, and PASI score were observed by other investigators 29,31,32, however, the significant positive correlation of CIMT with MPV in psoriatic patients was not reported in other studies till now.
Among platelet secreted cytokines are IL-1 and IL-8, which of particular interest to psoriasis research 25. Although in atherosclerosis, platelets produced IL-1, does not only activate endothelial cells 33, but also, induces the IL-6 and IL-8 production from vascular smooth muscle cells as well as their proliferation 34.
Regarding IL-1α and IL-6 serum levels, results of the conducted study revealed significant increase in both IL-1α and IL-6 serum concentrations in our psoriasis patients than their matched controls. These results were in parallel with that of Prens et al.35 and de Oliveria et al.36. Moreover, we observed significant positive correlation between both levels, and each of them with PASI score in our studied psoriatic cases, this finding was explained by Crome et al.37, who reported that IL-6 can induce IL-1α expression which promotes keratinocyte proliferation. Overexpression of proinflammatory IL-1α and IL-1β is positively correlated with symptom exacerbation and disease progression in psoriasis 38–40.
Here in, these IL-1α and IL-6 elevated concentrations were significantly correlated with both PASI score and CIMT at the same time. So, in agreement with Hansson 41, we can suggest that activation of the inflammatory process and up regulation of IL-1α and IL-6, Th-1 mediated cytokines, may be a possible cause of cardiac events and psoriasis together.
Furthermore, IL-1α and IL-6 concentrations were significantly correlated with MPV, a marker of platelet activity, in our study. Therefore, platelets role in pathogenesis of atherosclerosis may be mediated through proinflammatory IL-1α and IL-6 cytokines overexpressed in psoriasis patients.
Psoriasis is a risk factor for subclinical atherosclerosis, in addition platelets play a role in aetiopathogensis of psoriasis, and may be an imperative participant in the development of long-term macrovascular and microvascular complications determined by upregulations of IL-1α and IL-6 in this disease. MPV may be a better predictive biomarker for atherosclerosis in psoriatic patients.
We recommend, to address limitations of this study, large-scaled studies to validate current findings, and elucidate how platelet activity could contribute to increasing atherosclerotic risk in patients with psoriasis. Moreover, the use of antiplatelet medications in psoriasis management to reduce vascular and tissue injury which may decrease atherosclerotic risk is also recommended for future study.
Conflicts of interest
There are no conflicts of interest.
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Keywords:© 2018 Egyptian Women's Dermatologic Society
atherosclerosis; carotid intima media thicknes; interleukin-1; interleukin-6; mean platelet volume; predictive biomarker; psoriasis