Efficacy of Interferon-Gamma Treatment in Bronchial Asthma

Kim, Kwan Hyoung; Kim, Seok Chan; Kim, Young Kyoon; Kwon, Soon Seog; Kim, Chi Hong; Moon, Hwa Sik; Song, Jung Sup; Park, Sung Hak; Lee, Choong Eon; Byun, Kwang Ho

Abstract

BACKGROUND: There have been many in vitro evidences that interleukin-4(IL-4) might be the most important cytokine inducing IgE synthesis from B-cells, and interferon-gamma(IFN-gamma) might be a main cytokine antagonizing IL-4-mediated IgE synthesis. Recently some reports demonstrated that IFN-gamma might be used as a new therapeutic modality in some allergic diseases with high serum IgE level, such as atopic dermatitis or bronchial asthma. To evaluate the in vivo, effect of IFN-gamma in bronchial asthma we tried a clinical study.
METHODS
Fifty bronchial asthmatics(serum, IgE level over 200 IU/ml) who did not respond to inhaled or systemic corticosteroid treatment, and 17 healthy nonsmoking volunteers were included in this study. The CD 23 expressions of peripheral B-cells, the IL-4 activities of peripheral T-cells, the serum soluble CD23(sCD23) levels, and the superoxide anton(O2-) generations by peripheral PMN were compared between bronchial asthmatics and normal subjects. The IL-4 activities of peripheral T-cells were analyzed by T-cell supernatant (T-sup)-induced CD23 expression from tonsil B-cells. In bronchial asthmatics the serum IgE levels and histamine PC. in addition to the above parameters were also compared before and after IFN-gamma treatment. IFN-gamma was administered subcutaneously with a weekly dose of 30,000 IU per kilogram of body weight for 4 weeks.
RESULTS
The O2-, generations by peripheral PMNs in bronchial asthmatics were higher than normal subjects(8.23+/-0.94 vs 5.00+/-0.68 nmol/l x10(6) cells, P<0.05), and significantly decreased after IFN-gamma treatment compared to initial values(3.69+/-0.88 vs 8.61 +/- 1.53 nmol/l x 106 cells, P<0.05). CD23 expression of peripheral B-cells in bronchial asthmatics was higher than normal subjects(47.47 +/- 2.96% vs 31.62+/-1.92%, P<0.05), but showed no significant change after IFN-gammatreatment. The serum sCD23 levels in bronchial asthmatics were slightly higher than normal subjects( 191.04+/-23.3 U/ml vs 162.85+/-4.85 U/ml). and 11(64.7%) of 17 patients showed a decreasing pattern in their serum sCD23 levels after IFN-gamma treatment. However the means of serum sCD23 levels were not different before and after IFN-gamma treatment The IL-4 activities of peripheral T-cells in bronchial asthmatics were slightly higher than normal subjects 22.48 +/-6.81% vs 18.90+/-2.43%), and slightly increased after IFN-gamma treatment(27.90+/-2.56%). Nine(60%) of 15 patients showed a decreasing pattern in their serum IgE levels after IFN-gamma treatment. And the levels of serum IgE were significantly decreased after LEN-y treatment compared to initial values (658.67 +/- 120.84 IU/ml vs 1394.32 +/- 31442 IU/ml, P<0.05). Ten(83.3%) of 12 patients showed an improving pattern in bronchial hyperresponsiveness after IFN-gamma treatment, and the means of histamine PC20 were significantly increased after IFN-gamma treatment compared to initial values (1.22+/-0.29mg/ml vs 0.69+/-0.17mg/ml P<0.05).
CONCLUSION
Our results suggest that IFN-gamma may k useful as well as safety in the treatment of bronchial asthmatics with high serum IgE level and that in vivo effects of IFN-gamma may be different from its in vitro effects on the regulations of IgE synthesis or the respiratory burst of PMN.