Cytokine Patterns Associated with Bronchial Asthma in Saudi Patients

  

    
Groups of Age/ Year
    
IL5 (pg/ml)
  
  
 
  
 
  

    
Number
    
Moderate
    
Number
    
Severe
    

  
  

    
M±SD
    
Range
    
M±SD
    
Range
    
P value
  
  

    
(0- <10)
    
5
    
5.68±1.91
    
3.04– 7.85
    
7
    
5.50±1.74
    
3.11– 8.08
    
0.807
  
  
 
  

    
(10- <20)
    
6
    
5.11±1.45
    
3.11-7.31
    
4
    
5.86±2.42
    
4.41-9.47
    
0.67
  
  
 
  

    
(20- <30)
    
6
    
3.99±1.68
    
2.58- 7.23
    
4
    
4.14±0.75
    
3.27- 5.09
    
0.388
  
  

    
(30- <40)
    
5
    
3.57±0.49
    
2.66– 5.09
    
4
    
4.08±0.79
    
3.34– 5.17
    
0.217
  
  
 
  

    
(40- <50)
    
4
    
4.33±1.58
    
2.89- 6.24
    
4
    
3.99±1.27
    
2.89- 5.78
    
0.885
  
  
 
  

    
(50- <60)
    
5
    
3.51±1.34
    
2.43- 5.86
    
4
    
3.84±1.35
    
2.81- 5.70
    
0.999
  
  

    
( =60 )
    
7
    
3.46±0.73
    
2.89 – 4.86
    
5
    
3.80±1.52
    
2.36 –5.93
    
0.999
  
  

    
Total
    
38
    
4.24±1.38
    
2.43-7.85
    
32
    
4.46±1.40
    
2.36 -9.47
    
0.385
  

Table 10: Comparison between serum IL-5 levels in moderate and severe asthmatic patients in different age groups.

The highest concentrations of IL-5 in moderate and severe were found in young age groups (0-<10) and (10-<20) respectively. Comparison between total IL-5 concentrations the results indicated no significant differences between moderate and severe asthmatic patients.

Discussion

The pathophysiological basis underlying reversible airway obstruction in bronchial asthma is inflammation [9]. Many studies have suggested that the severity of asthma is related to the degree of inflammation [10,11]. Animal models and clinical studies in humans have indicated an important role for Th2 cells producing IL-4 and IL-5 in the pathogenesis of allergic asthma [5], with the induction of a Th1 response that seems to aggravate an inflammatory process [6].

The results of our study proved that the levels of serum IL-4 and IL-5 in asthmatic patients agreed to some extent with the results published before, which demonstrated that both pro-inflammatory and Th2 cytokines play critical roles in the inflammatory characteristics of allergic asthma. Our results indicated that serum IL-4 was significantly higher in asthmatic patients than in healthy individuals. Comparison of the study results between the groups (moderate, severe asthma, and control) evidenced that serum concentrations of IL-4 in the group with moderate (p<0.001) and severe asthma (p<0.001) were statisti cally significantly higher in comparison to the group with control. These results might be indicative of different degrees of the disease (disease severity) with their underlying degrees of chronic inflammation also being different and IL-4 as possible markers. Moreover, other data proved that IL-4 is necessary for the differentiation of the naive CD-positive T-cells within the Th2 subpopulation secreting IL-4 and IL-5. Although IL-4 induces IgE synthesis and enables the immediate type of hypersensitivity reaction, there is certain evidence suggesting in vitro and in vivo anti-inflammatory effects of IL-4. IL-4 is critical in switching B lymphocytes to produce IgE, for expression of Vascular Cell Adhesion Molecules-1 (VCAM-1) on endothelial cells. IL-4 is of critical importance in the differentiation of Th2 cells and is therefore an 'upstream' cytokine that is an attractive therapeutic target in the treatment of atopic diseases. My results agree with those that proved that excessive IL-4 production by Th2 cells has been associated with elevated allergy [12]. Other results demonstrated that Th1/Th2 imbalance results in the clinical expression of allergy and/or asthma. Studies on mice and humans have shown Th2 cytokines [IL-4 and IL-5] as major contributors to allergy and asthma. In those studies, serum IL-4 was below detectable level in all the subjects, those results disagreed with our results. Nevertheless, IL-5, an IgE-stimulating cytokine was associated with bronchial asthma in children.

It has been reported that IL-5 has a critical role in eosinophilia which has been confirmed by the use of an anti-IL-5 antibody in asthmatic patients, which almost depletes circulating eosinophils and prevents eosinophil recruitment into the airway after allergen. IL-5 is a cytokine that is not encountered at high levels in healthy individuals. Control of IL-5 protein production takes place at the level of transcription [13]. IL-10 is a potent anti-inflammatory cytokine that inhibits the synthesis of many inflammatory proteins, including cytokines (TNF-a, granulocyte-macrophage colony-stimulating factor, IL-5, chemokines) and inflammatory enzymes (inducible nitric oxide synthesis) that are over-expressed in asthma [14].

Our finding showed elevation of serum IL-5 in asthmatic patients concurs with previous reports that there are significantly lower IL-5 serum concentrations in the group of healthy controls in comparison to the group with bronchial asthma. Comparison of the study results between the groups (moderate, severe asthma, and control) evidenced that serum concentrations of IL-5 in the group with moderate (p<0.001) and severe asthma (p<0.001) were statistically significantly higher in comparison to the group with control. However, no significant differences (p=0.385) have been detected between the groups of severe and moderate cases.

These finding are in agreement with many other results applied for measurements of IL-5. Motojima et al [15] determined IL-5 serum concentrations in 78 asthma patients (the control group comprised 30 healthy individuals). Results of the study revealed that IL-5 serum concentration in asthma patients was statistically significantly higher in comparison to IL-5 concentration values in the healthy controls.

A comparison of the study results between the groups (mild, moderate, and severe asthma) shows that IL-5 serum concentrations are significantly higher in the group with moderate and severe asthma in comparison to the group with mild asthma. Serum concentrations in patients with moderate and severe asthma were significantly higher in comparison to those obtained in the group with mild asthma. The study conducted by Hacken et al [16] also verified significantly higher IL-4 and IL-5 serum concentrations in 17 patients with asthma in comparison to concentrations of the cytokines in healthy controls, however, they have failed to evidence correlation between IL-4 and IL-5 concentrations and parameters of clinical manifestations of asthma.

The lack of significant difference in IL-4 and IL-5 serum concentrations between patients with moderate and severe asthma supports the attitudes of the majority of different authors considering that the groups with these forms of asthma may be practically treated during the studies as one common group of patients with prominent and advanced inflammation which is significantly different from inflammation found in mild asthma.

It may be concluded that the results of our study are consistent with other results reported so far, suggesting that cytokines IL-4 and IL-5 obviously represent good markers of chronic inflammation of the lower airways in bronchial asthma. Their application for the diagnostic as well as predictive purpose may be reasonably recommended, however only within the research projects for the time being. Additional studies on the role of IL-4 and IL-5 in chronic inflammation associated with asthma are needed.

Comparison between different age groups (10-<20), (20-<30), (30-<40), (40-<50), (50-<60), and (= 60) years indicated higher serum cytokines levels in young age groups than elderly in many cases whereas no significant differences have been found in middle age groups. Serum IL-4 concentrations in severe asthmatic patients in the age group (= 60) were statistically significantly lower in comparison to the age group (0-<10) (p=0.009), age group (20-<30) (p=0.027), age group (30-<40) (p=0.036) and age group (40-<50) (p=0.048). Serum IL-5 concentrations in moderate asthmatic patients in the age group (= 60) were statistically significantly lower in comparison to the age group (0-<10) (p=0.042) and age group (10-<20) (p=0.032).

These observations are in agreement to some extent with the findings of other investigators as Drazen J [17] who shows that asthma approximately affects 5% of the adult population, most cases begin before the age of 25 years but it may develop at any time through life. Other studies conducted by Sudha S Deo et al [18], observed the pattern of cytokines in patients with asthma most of them were in the age group 25-45 years. Age differences in different groups were not seen. There was also no significant difference as far as the duration of the disease was concerned.

Conclusion

This study showed that total serum levels of Th2 cytokines are elevated in asthmatic patients which may be responsible for the pathological features of asthma. The role of age in the development of disease symptoms may be uncertain with a tendency to occur in young ages more frequently than elderly which may be due to that most cases have onset before the age of 25 years, but it may develop at any time through life. Finally, additional studies may be recommended to demonstrate the use of anti-cytokine therapy which may help in treating inflammatory diseases for asthmatic patients.

Author Statements

Conflict of Interest

The authors declare that is no conflict interest.

Authors contribution

All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.

Data Availability

All datasets generated or analyzed during this study are included in the manuscript.

Ethics Statement

This study was approved by the institutional review board (IRB 23-091) of the General Directorate of Health Affairs in Madinah.

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