Augmentation of leukotriene C4 production by gamma interferon in leukocytes challenged with an allergen

Leukocytes from mite-sensitive asthmatic patients were challenged with an allergen and the supernatant assayed for histamine, immunoreactive leukotriene C4 (i-LTC4), and gamma-interferon (gamma-IFN). In addition, the concentration of gamma-IFN in the plasma of patients with bronchial asthma was assayed. Significantly higher concentrations (p less than 0.01) of gamma-IFN were detected in patients' plasma (0.27 +/- 0.32 U/ml, n = 61) than in that of healthy controls (0.04 +/- 0.06 U/ml, n = 19). The leukocytes produced 7.3 +/- 6.7 ng of i-LTC4/10(6) basophils (n = 32), and histamine release was 41.1 +/- 37.1% of total histamine. There was a significant correlation (p less than 0.01) between the capacity of leukocytes to release i-LTC4 and gamma-IFN. The capacity of leukocytes to release histamine and to produce gamma-IFN was not significantly correlated (r = 0.263). About twice as much i-LTC4 was generated from leukocytes pretreated for 24 h with 0.1-1.0 U/ml of recombinant human gamma-IFN, but histamine release was not changed. Another type of IFN, alpha-IFN, did not alter the capacity of leukocytes to release histamine as well as gamma-IFN upon preincubation for 24 h at 1-1,000 U/ml. Pretreatment with 1-10 U/ml of beta-IFN slightly enhanced the capacity upon challenge with 10 ng/ml of mite allergen. The enhancing effect of gamma-IFN on i-LTC4 generation was decreased by treatment with H-7, a nonspecific inhibitor of protein kinase C activity.(ABSTRACT TRUNCATED AT 250 WORDS)