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)
Saito
H
H
Clinical Research Center for Rheumato-Allergology, National Sagamihara Hospital, Japan.
Hayakawa
T
T
Mita
H
H
Yui
Y S
YS
Shida
T
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors; D016861:Cyclooxygenase Inhibitors; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood / Q000494:pharmacology*; D007962:Leukocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D008925:Mites / Q000276:immunology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013189:SRS-A / Q000096:biosynthesis* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000485:Allergens; D001095:Arachidonic Acids; D002147:Calmodulin; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D013189:SRS-A; D016718:Arachidonic Acid; D007371:Interferon-gamma; D011493:Protein Kinase C