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The profile of the key pro-inflammatory cytokines in the serum of patients with CD and their association with the disease severity and activity | BMC Gastroenterology


The mean age of CD diagnosis in examined patients was (27.75 ± 3.62) years.

The study of the features of CD clinical course showed that the most typical symptoms for the included patients were asthenia-vegetative being observed in 61 people(100.0%), abdominal pain in 55 people (90.2%), flatulence in 46 people (75.4%), diarrhea/frequent stool in 40 people (65.6%), an admixture of mucus and/or blood in stool in 32 people (52.5%), weight loss in 39 people (63.9%), increased body temperature in 37 people (60.7%). Besides, 30 patients (49.2%) with CD had extraintestinal manifestations, among which joint lesions were in 13 (21.3%) patients, skin lesions in 10 patients (16.4%), gallstone disease in 8 patients (13.1%), urolithiasis in 7 patients (11.5%), and eye lesions in 7 patients (11.5%). It should be noted that among 30 patients (49.2%), extraintestinal symptoms with involvement of several organs and organ systems were recorded in 16 patients (53.3%, Table 1).

Table 1 Distribution of clinical symptoms and disease activity (according to CDAI) in patients with Crohn’s disease (n = 61)

When analyzing the CDAI values, 18 patients (29.5%) corresponded to low disease activity, 37 patients (60.7%) had moderate activity, and high activity of the disease was noted in 6 (9.8%) patients. The mean CDAI value in patients was (346.90 ± 25.37) points, which corresponds to a moderate degree of disease severity. Besides, CDAI was higher in persons with a combined involvement of the large and small intestine lesions than those with terminal ileitis or isolated involvement of the large intestine.

Compared to healthy people, the study of the pro-inflammatory cytokines content in the blood of CD patients showed an increase in the following proteins (Table 2): TNF-α increased 4.45-fold (137.46 ± 9.72 vs. 30.88 ± 2.08 pg/ml in healthy people, p < 0.001), IL-1α – 5.08-fold (51.55 ± 4.36 vs. 10.14 ± 0.93 pg/ml, p < 0.001), IL-6 – 2.16-fold (20.03 ± 1.81 vs. 9.27 ± 0.52 pg/ml, p < 0.001), IL-8 – 2.04-fold (25.74 ± 2.05 vs. 12.62 ± 1.16 pg/ml, p < 0.001), and INF-γ – 5.30-fold (208.63 ± 14.29 vs. 39.35 ± 2.40 pg/ml, p < 0.001).

Table 2 Serum levels of pro-inflammatory cytokines in patients with Crohn’s disease, (M ± SD)

It has been established that the blood content of the pro-inflammatory cytokines increased with higher disease activity (CDAI). In particular, TNF-α content in the blood of patients with low cytokines activity was 3.34 times higher than that in healthy people (p < 0.001), with moderate activity – by 4.41 times (p < 0.001), with high activity – by 5.70 times (p < 0.001). At that, the content of this cytokine in persons with moderate disease activity was 1.32 times (p < 0.005) higher than in persons with low activity, 1.30 times (p < 0.005) higher in persons with moderate disease activity, 1.71 times (p < 0.001) higher in persons with low activity of the disease (Fig. 1).

Fig. 1

TNF-α content (pg/ml) in blood serum of patients with Crohn’s disease as a function of the disease activity stage. Note. The «▬» sign in chart blocks denotes the mean value of indicators

A similar trend was observed for the IFN-γ content in the blood. Thus, this indicator was 4.24 times (p < 0.001) higher than in persons with low disease activity than in healthy people, 5.08 times higher (p < 0.001), in those with moderate activity, and 5.99 times higher in patients with highly active disease course (p < 0.001). At that, IFN-γ content in people with moderate activity was 1.28 times (p < 0.005) higher compared to patients with low disease activity, and those with high activity had 1.20 times (p < 0.005) higher content compared to moderate activity and 1.54 times (p < 0.005) higher compared to low activity (Fig. 2).

Fig. 2
figure 2

The INF-γ content (pg/ml) in blood serum of patients with Crohn’s disease as a function of the disease activity stage. Note. The «▬» sign in chart blocks denotes the mean value of indicators

IL-1α content was 3.65 times (p < 0.001) higher in those with low disease activity, 5.00 times (p < 0.001) with moderate activity, and 6.14 times (p < 0.001) with high activity, respectively. In those with moderate CD activity, this cytokine content was 1.37 times (p < 0.001) higher than by low activity higher than in low activity, and in patients with high activity – 1.27 times (p < 0.001) higher than with moderate activity and 1.73 times (p < 0.001) higher than with low activity (Fig. 3).

Fig. 3
figure 3

The IL-1α content (pg/ml) in blood serum of patients with Crohn’s disease as a function of the disease activity stage. Note. The «▬» sign in chart blocks denotes the mean value of indicators

Compared to healthy people, the IL-6 content in the blood of patients with low disease activity was 1.96 times higher (p < 0.001), with moderate activity – 2.15 times higher (p < 0.001), and with high activity – 2.55 times (p < 0.001) (Fig. 4). The content of IL-8 was 1.68 (p < 0.005), 1.96 (p < 0.005), and 2.39 times higher (p < 0.001) higher, respectively (Fig. 5). Patients with high CD activity demonstrated 1.31 times higher (p < 0.005) IL-6 blood content compared to patients with low disease activity and 1.43 times higher (p < 0.005) IL-8 content compared to patients with low disease activity, respectively.

Fig. 4
figure 4

The IL-6 (pg/ml) in blood serum of patients with Crohn’s disease as a function of the disease activity stage. Note. The «▬» sign in chart blocks denotes the mean value of indicators

Fig. 5
figure 5

The IL-8 content (pg/ml) in blood serum of patients with Crohn’s disease as a function of the disease activity stage. Note. The «▬» sign in chart blocks denotes the mean value of indicators

The following correlations have been established: between the CD activity index and the content of TNF-α (r = 0.84, p < 0.013), INF-γ (r = 0.61, p < 0.028); between TNF-α and INF-γ content (r = 0.67, p < 0.023), IL-1α (r = 0.49, p < 0.042), IL-6 (r = 0.40, p < 0.045), and IL-8 (r = 0.51, p < 0.033); INF-γ and IL-1α (r = 0.53, p < 0.040), IL-6 (r = 0.37, p < 0.039), IL-8 (r = 0.44, p < 0.040); IL-1α and IL-6 (r = 0.55, p < 0.045), IL-8 (r = 0.36, p < 0.038); IL-6 and IL-8 (r = 0.60, p < 0.020).



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