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Background: The relation between interleukin-33 (IL-33) and asthma is not precisely known yet. The present study set to compare the serum level of IL-33 in patients with asthma and controls and study the relation with the severity of disease. Methods: The serum level of IL-33 and total IgE in 89 asthmatic patients and 57 controls were analyzed. The association of levels of IL-33 with the severity of disease, levels of total IgE, measures of spirometry (forced expiratory volume in 1 s [FEV1]), age, sex, presence or absence of other allergic diseases, and the disease duration was evaluated. Results: Higher levels of IL-33 and total IgE were detected in asthmatic patients compared with controls (P = 0.0001 and P = 0.008, respectively). In the asthmatic group, a significant direct association of IL-33 with age (P = 0.02, R = 0.23) and with total IgE level (P = 0.003, R = 0.31) were observed, but there was no relationship between other variables. Comparison of mean level of IL-33 in different asthma groups concerning the disease severity showed the statistically significant difference between them and a significant increased serum level of total IgE was observed in more severe disease. The results showed a significant negative correlation between FEV1 and total IgE (P = 0.028, R = -0.23) and IL-33 level (P = 0.0001, R = -0.83). Conclusions: IL-33 is suggested as a new inflammatory marker of severe and refractory asthma. Therefore, it may be a unique therapeutic target in these patients. [ABSTRACT FROM AUTHOR]