Augmentation of Leukotriene C4 Production by Gamma Interferon in Leukocytes Challenged with an Allergen

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Leukocytes from mite-sensitive asthmatic patients were challenged with an allergen and the supernatant assayed for histamine, immunoreactive leukotriene C4 (i-LTC4), and γ-interferon (γ-IFN). In addition, the concentration of γ-IFN in the plasma of patients with bronchial asthma was assayed. Significantly higher concentrations (p <0.01) of γ-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-LTC4/106 basophils (n = 32), and histamine release was 41.1 ± 37.1% of total histamine. There was a significant correlation (p <0.01) between the capacity of leukocytes to release i-LTC4 and γ-IFN. The capacity of leukocytes to release histamine and to produce γ-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 γ-IFN, but histamine release was not changed. Another type of IFN, α-IFN, did not alter the capacity of leukocytes to release histamine as well as γ-IFN upon preincubation for 24 h at 1–1,000 U/ml. Pretreatment with 1–10 U/ml of β-IFN slightly enhanced the capacity upon challenge with 10 ng/ml of mite allergen. The enhancing effect of γ-IFN on i-LTC4 generation was decreased by treatment with H-7, a nonspecific inhibitor of protein kinase C activity. The capacity of leukocytes to produce γ-IFN and i-LTC4 was enhanced by treatment with phorbol myristate acetate. W-7, a calmodulin antagonist, dose dependency inhibited the production of both γ-IFN and i-LTC4 in the allergen-stimulated leukocytes. AA-861, a selective inhibitor of 5-lipoxygenase, inhibited the production of both γ-IFN and i-LTC4. From these findings, it is assumed that the activation of protein kinase C by treatment with γ-IFN is closely related to the enhancement of i-LTC4 production. In addition, the generation of 5-lipoxygenase products, such as i-LTC4, is closely connected with the production of γ-IFN in allergen-stimulated leukocytes.