Our study showed a tendency that local and systemic IL-22 level was increased in patients with allergic airway diseases caused by HDM. Both, IL-22 level in serum and IL-22 level in nasal lavage were positively associated with IL-10 level in serum and nasal lavage. Our findings support hypothesis of anti-inflammatory effect of IL-22 in persistent allergic airway diseases. However, experimental, and clinical studies provide controversial data about possible role of IL-22 in these diseases (14, 21).
Our findings are in agreement with the majority of clinical studies investigating IL-22 level in patients with allergic rhinitis and/ or allergic asthma and revealed that concentration of IL-22 in serum or plasma was higher in these patients than in healthy subjects (22–27). Though, studies investigating local IL-22 level provided controversial results. For example, Shahsavan found that the gene expression level of IL-22 in human nasal mucosa was higher in patients with persistent allergic rhinitis than in healthy individuals (23). In contrary, Andersson et al. analysed IL-22 level in childrens’ with severe asthma bronchoalveolar lavage and did not found differences between asthma group and control group (26). However, there are more evidence that IL-22 level is higher in patients with allergic airway diseases. Differences between studies can occur due to relatively small studies samples and different methods used for investigation of IL-22 level.
In our study level of IL-22 was positively related with IL-10, despite local or systemic. This supports hypothesis of anti-inflammatory effect of IL-22. We found positive correlation between local and systemic IL-22 level and local and systemic IL-10 level. We did not find any clinical study investigating relationship between IL-22 and other proinflammatory and anti-inflammatory cytokines in allergic airway diseases in PubMed database. But experimental studies revealed that IL-22-positive mice had a lower level of IL-13 in the bronchoalveolar lavage after ovalbumin stimulation in comparison with IL-22-negative mice (28, 29). Nakagome et al. showed that IL-22-producing plasmid vector that was delivered before the sensitization with ovalbumin suppressed eosinophilic airway inflammation and increased the level of IL-10 (30). However, other study showed that ovalbumin-challenged and IL-22-deficient mice had low level of IL-5, IL-13 and IL-33 (31). It is thought that IL-22 plays its role via subsequent Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathways (32).
Our study showed that IL-22 level in nasal lavage negatively correlated with eosinophil count in nasal smear in patients with allergic rhinitis and allergic asthma. In contrary, Shahsavan et al. revealed positive link between serum IL-22 level and eosinophil count in nasal mucosa (23). However, IL-22 level in serum may not reflect the local IL-22 level and this could be the reason for controversial data. Some experimental studies showed that ovalbumin-challenged and IL-22-deficient mice had a low level of eosinophils in bronchoalveolar lavage and lung tissue and reduced leukocyte infiltration (31). In contrary, some other studies with animals reported that after ovalbumin stimulation IL-22-positive mice had a reduced number of eosinophils in the bronchoalveolar lavage when compared with IL-22-negative mice (28, 29). Moreover, Besnard et al. suggested that IL-22 may play dual role in allergic airway inflammation – it may be necessary for the induction of inflammation, but during continuous allergen challenge, the lack of IL-22 may exacerbate allergic inflammation (31). In contrary, Nakagome et al. presented that IL-22 could have an immunosuppressive effect during the early stage of an immune response by reducing eosinophilic airway inflammation (30). The differences between the results from different studies could be explained by different conditions and methods of experiments.
We did not find significant correlation between IL-22 in serum and IL-22 in nasal lavage. Interestingly, we found negative correlation between serum IL-22 level and IL-22 level in nasal lavage only in patients with allergic rhinitis together with allergic asthma. These findings suggest that systemic IL-22 level may not reveal local IL-22 concentration. We did not find other studies investigating relation between local and systemic IL-22 level in allergic airway diseases.
Our study revealed a negative link between serum IL-22 and RQLQ in patients with allergic airway diseases. In contrast, other two studies performed by Shahsavan et al. and Zhu et al. revealed positive relationship between serum IL-22 and rhinitis and asthma symptoms scores in patients with allergic rhinitis and allergic asthma (23, 25). Farfariello et al. found that IL-22 was higher in patients with severe allergic rhinitis and severe allergic asthma than in patients with moderate allergic rhinitis and allergic asthma (24). Zhao et al. also found that level of IL-22 in plasma was consistently increased with the severity of asthma (27). Moreover, Sherkat et al. showed a significantly higher level of IL-22 in serum and sputum samples from adults with severe asthma in comparison to patients with moderate asthma (33). These findings show that IL-22 depends on the disease severity. In contrast, Bayrak Degirmenci et al. did not find any relation between plasma IL-22 and symptoms score in patients with allergic rhinitis (22). As mentioned before, these differences between studies could be determined by relatively small studies samples, different methods of IL-22 investigation and use of different tools for investigating severity of symptoms.
To our knowledge, there are no published articles about IL-22 level in nasal lavage and relation between systemic and local IL-22 level and other cytokines. Moreover, there are lack of articles presenting data about IL-22 link with symptoms score, quality of life and different inflammatory markers in patients with allergic airway diseases.