Differential Regulation of Antigen-Induced IL-4 and IL-13 Generation From T Lymphocytes by IFN-α

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Background: IL-4 and IL-13 are related cytokines with similar functional properties. Differential regulation of IL-4 and IL-13 has not been described. Objective: We have examined the effects of IFN-α on antigen-driven proliferation, IL-4 generation, and IL-13 generation from human PBMCs and T-cell clones. Methods: Proliferation was assessed by 3H-thymidine incorporation. Cytokine generation was assessed by reverse transcription PCR and ELISA. Messenger RNA stability was assessed in the presence of actinomycin D. Results: IFN-α induced a concentration-dependent inhibition of antigen-driven proliferation of TH1 and TH2 clones (median effective concentration, 150 to 200 U/mL); the sensitivity of TH1 and TH2 clones to IFN-α was not significantly different (P = .6). IFN-α induced an analogous concentration-dependent inhibition of antigen-driven IL-13 generation from TH1 and TH2 clones (median effective concentration, 100 U/mL); this effect was evident by 12 hours of culture and persisted beyond 48 hours. However, IL-4 generation from TH2 clones was insensitive to IFN-α at all concentrations and times tested (1 to 10,000 U/mL). A similar inhibitory effect of IFN-α on mitogen-driven proliferation and IL-13 generation from PBMCs was demonstrated; once again, IL-4 generation from PBMCs was insensitive to IFN-α. IL-13 mRNA stability was unaffected by IFN-α, suggesting transcriptional regulation. Conclusion: IFN-α differentially regulates antigen-stimulated IL-4 and IL-13 generation.