IL-4 inhibits the costimulatory activity of IL-2 or picolinic acid but not of lipopolysaccharide on IFN-γ-treated macrophages

George W. Cox, Utpala Chattopadhyay, Joost J. Oppenheim, Luigi Varesio

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Abstract

We reported previously that IL-2 induces tumoricidal activity in IFN-γ-treated murine macrophages. The present study was performed to investigate the regulation of IL-2-dependent tumoricidal activity in murine macrophage cell lines. The v-raf/v-myc-immortalized murine macrophage cell lines ANA-1, GG2EE, and HEN-CV did not express constitutive levels of cytotoxic activity against P815 mastocytoma cells. Moreover, these macrophage cell lines did not become tumoricidal after exposure to IL-4, IFN-γ, IL-2 or LPS. However, these macrophages developed cytotoxic capabilities after incubation with either IFN-γ plus IL-2 or IFN-γ plus LPS. IL-4 inhibited IFN-γ plus IL-2- but not IFN-γ plus LPS-induced tumoricidal activity. This effect of IL-4 was not restricted to v-raf/v-myc-immortalized macrophage cell lines because similar results were obtained by using a macrophage cell line that was established from a spontaneous histiocytic sarcoma. The suppressive activity of IL-4 on the ANA-1 macrophage cell line was dose-dependent (approximately 12-200 U/ml) and was neutralized by the addition of anti-IL-4 mAb. IL-4 decreased the IFN-γ-induced expression of mRNA for the p55 (α) subunit of the IL-2R in ANA-1 macrophages. Therefore, at least one mechanism by which IL-4 may have inhibited IFN-γ plus IL-2-induced tumoricidal activity was by reducing macrophage IL-2Rα mRNA expression. We have previously reported that picolinic acid, a tryptophan metabolite, is a costimulator of macrophage tumoricidal activity. We now report that IL-4 also inhibited IFN-γ plus picolinic acid-induced cytotoxicity in ANA-1 macrophages. We propose that IL-2 and picolinic acid may have a common mechanism of action that is susceptible to IL-4 suppression.

Original languageEnglish
Pages (from-to)3809-3814
Number of pages6
JournalJournal of Immunology
Volume147
Issue number11
Publication statusPublished - Dec 1 1991

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Interleukin-4
Interleukin-2
Lipopolysaccharides
Macrophages
Cell Line
picolinic acid
Histiocytic Sarcoma
Mastocytoma
Messenger RNA
Tryptophan

ASJC Scopus subject areas

  • Immunology

Cite this

IL-4 inhibits the costimulatory activity of IL-2 or picolinic acid but not of lipopolysaccharide on IFN-γ-treated macrophages. / Cox, George W.; Chattopadhyay, Utpala; Oppenheim, Joost J.; Varesio, Luigi.

In: Journal of Immunology, Vol. 147, No. 11, 01.12.1991, p. 3809-3814.

Research output: Contribution to journalArticle

Cox, George W. ; Chattopadhyay, Utpala ; Oppenheim, Joost J. ; Varesio, Luigi. / IL-4 inhibits the costimulatory activity of IL-2 or picolinic acid but not of lipopolysaccharide on IFN-γ-treated macrophages. In: Journal of Immunology. 1991 ; Vol. 147, No. 11. pp. 3809-3814.
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abstract = "We reported previously that IL-2 induces tumoricidal activity in IFN-γ-treated murine macrophages. The present study was performed to investigate the regulation of IL-2-dependent tumoricidal activity in murine macrophage cell lines. The v-raf/v-myc-immortalized murine macrophage cell lines ANA-1, GG2EE, and HEN-CV did not express constitutive levels of cytotoxic activity against P815 mastocytoma cells. Moreover, these macrophage cell lines did not become tumoricidal after exposure to IL-4, IFN-γ, IL-2 or LPS. However, these macrophages developed cytotoxic capabilities after incubation with either IFN-γ plus IL-2 or IFN-γ plus LPS. IL-4 inhibited IFN-γ plus IL-2- but not IFN-γ plus LPS-induced tumoricidal activity. This effect of IL-4 was not restricted to v-raf/v-myc-immortalized macrophage cell lines because similar results were obtained by using a macrophage cell line that was established from a spontaneous histiocytic sarcoma. The suppressive activity of IL-4 on the ANA-1 macrophage cell line was dose-dependent (approximately 12-200 U/ml) and was neutralized by the addition of anti-IL-4 mAb. IL-4 decreased the IFN-γ-induced expression of mRNA for the p55 (α) subunit of the IL-2R in ANA-1 macrophages. Therefore, at least one mechanism by which IL-4 may have inhibited IFN-γ plus IL-2-induced tumoricidal activity was by reducing macrophage IL-2Rα mRNA expression. We have previously reported that picolinic acid, a tryptophan metabolite, is a costimulator of macrophage tumoricidal activity. We now report that IL-4 also inhibited IFN-γ plus picolinic acid-induced cytotoxicity in ANA-1 macrophages. We propose that IL-2 and picolinic acid may have a common mechanism of action that is susceptible to IL-4 suppression.",
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