• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Oct 1987; 84(20): 7251–7255.
PMCID: PMC299269

Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells.


One of the oldest and most preserved of the homeostatic responses of the body to injury is the acute phase protein response associated with inflammation. The liver responds to hormone-like mediators by the increased synthesis of a series of plasma proteins called acute phase reactants. In these studies, we examined the relationship of hepatocyte-stimulating factor derived from peripheral blood monocytes to interferon beta 2 (IFN-beta 2), which has been cloned. Antibodies raised against fibroblast-derived IFN-beta having neutralizing activity against both IFN-beta 1 and -beta 2 inhibited the major hepatocyte-stimulating activity derived from monocytes. Fibroblast-derived mediator elicited the identical stimulated response in human HepG2 cells and primary rat hepatocytes as the monocyte cytokine. Finally, recombinant-derived human B-cell stimulatory factor type 2 (IFN-beta 2) from Escherichia coli induced the synthesis of all major acute phase proteins studied in human hepatoma HepG2 and primary rat hepatocyte cultures. These data demonstrate that monocyte-derived hepatocyte-stimulating factor and IFN-beta 2 share immunological and functional identity and that IFN-beta 2, also known as B-cell stimulatory factor and hybridoma plasmacytoma growth factor, has the hepatocyte as a major physiologic target and thereby is essential in controlling the hepatic acute phase response.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Tillett WS, Francis T. SEROLOGICAL REACTIONS IN PNEUMONIA WITH A NON-PROTEIN SOMATIC FRACTION OF PNEUMOCOCCUS. J Exp Med. 1930 Sep 30;52(4):561–571. [PMC free article] [PubMed]
  • Kushner I. The phenomenon of the acute phase response. Ann N Y Acad Sci. 1982;389:39–48. [PubMed]
  • Kampschmidt RF. Leukocytic endogenous mediator. J Reticuloendothel Soc. 1978 Apr;23(4):287–297. [PubMed]
  • Bornstein DL. Leukocytic pyrogen: a major mediator of the acute phase reaction. Ann N Y Acad Sci. 1982;389:323–337. [PubMed]
  • Dinarello CA. Interleukin-1. Rev Infect Dis. 1984 Jan-Feb;6(1):51–95. [PubMed]
  • Le J, Vilcek J. Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest. 1987 Mar;56(3):234–248. [PubMed]
  • Gauldie J, Sauder DN, McAdam KP, Dinarello CA. Purified interleukin-1 (IL-1) from human monocytes stimulates acute-phase protein synthesis by rodent hepatocytes in vitro. Immunology. 1987 Feb;60(2):203–207. [PMC free article] [PubMed]
  • Koj A, Kurdowska A, Magielska-Zero D, Rokita H, Sipe JD, Dayer JM, Demczuk S, Gauldie J. Limited effects of recombinant human and murine interleukin 1 and tumour necrosis factor on production of acute phase proteins by cultured rat hepatocytes. Biochem Int. 1987 Mar;14(3):553–560. [PubMed]
  • Baumann H, Onorato V, Gauldie J, Jahreis GP. Distinct sets of acute phase plasma proteins are stimulated by separate human hepatocyte-stimulating factors and monokines in rat hepatoma cells. J Biol Chem. 1987 Jul 15;262(20):9756–9768. [PubMed]
  • Darlington GJ, Wilson DR, Lachman LB. Monocyte-conditioned medium, interleukin-1, and tumor necrosis factor stimulate the acute phase response in human hepatoma cells in vitro. J Cell Biol. 1986 Sep;103(3):787–793. [PMC free article] [PubMed]
  • Perlmutter DH, Dinarello CA, Punsal PI, Colten HR. Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression. J Clin Invest. 1986 Nov;78(5):1349–1354. [PMC free article] [PubMed]
  • Ramadori G, Sipe JD, Dinarello CA, Mizel SB, Colten HR. Pretranslational modulation of acute phase hepatic protein synthesis by murine recombinant interleukin 1 (IL-1) and purified human IL-1. J Exp Med. 1985 Sep 1;162(3):930–942. [PMC free article] [PubMed]
  • Ritchie DG, Fuller GM. An in vitro bioassay for leukocytic endogenous mediator(s) using cultured rat hepatocytes. Inflammation. 1981 Dec;5(4):275–287. [PubMed]
  • Koj A, Gauldie J, Regoeczi E, Sauder DN, Sweeney GD. The acute-phase response of cultured rat hepatocytes. System characterization and the effect of human cytokines. Biochem J. 1984 Dec 1;224(2):505–514. [PMC free article] [PubMed]
  • Baumann H, Firestone GL, Burgess TL, Gross KW, Yamamoto KR, Held WA. Dexamethasone regulation of alpha 1-acid glycoprotein and other acute phase reactants in rat liver and hepatoma cells. J Biol Chem. 1983 Jan 10;258(1):563–570. [PubMed]
  • Koj A, Gauldie J, Sweeney GD, Regoeczi E, Sauder DN. A simple bioassay for monocyte-derived hepatocyte stimulating factor: increased synthesis of alpha 2-macroglobulin and reduced synthesis of albumin by cultured rat hepatocytes. J Immunol Methods. 1985 Feb 11;76(2):317–327. [PubMed]
  • Woloski BM, Fuller GM. Identification and partial characterization of hepatocyte-stimulating factor from leukemia cell lines: comparison with interleukin 1. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1443–1447. [PMC free article] [PubMed]
  • Baumann H, Jahreis GP, Sauder DN, Koj A. Human keratinocytes and monocytes release factors which regulate the synthesis of major acute phase plasma proteins in hepatic cells from man, rat, and mouse. J Biol Chem. 1984 Jun 10;259(11):7331–7342. [PubMed]
  • Baumann H, Hill RE, Sauder DN, Jahreis GP. Regulation of major acute-phase plasma proteins by hepatocyte-stimulating factors of human squamous carcinoma cells. J Cell Biol. 1986 Feb;102(2):370–383. [PMC free article] [PubMed]
  • Weissenbach J, Chernajovsky Y, Zeevi M, Shulman L, Soreq H, Nir U, Wallach D, Perricaudet M, Tiollais P, Revel M. Two interferon mRNAs in human fibroblasts: in vitro translation and Escherichia coli cloning studies. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7152–7156. [PMC free article] [PubMed]
  • Sehgal PB, May LT, Tamm I, Vilcek J. Human beta 2 interferon and B-cell differentiation factor BSF-2 are identical. Science. 1987 Feb 13;235(4790):731–732. [PubMed]
  • Revel M, Zilberstein A. Interferon-beta 2 living up to its name. Nature. 1987 Feb 12;325(6105):581–582. [PubMed]
  • Jordana M, Newhouse MT, Gauldie J. Alveolar macrophage/peripheral blood monocyte-derived factors modulate proliferation of primary lines of human lung fibroblasts. J Leukoc Biol. 1987 Jul;42(1):51–60. [PubMed]
  • Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T, Kashiwamura S, Nakajima K, Koyama K, Iwamatsu A, et al. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature. 1986 Nov 6;324(6092):73–76. [PubMed]
  • May LT, Helfgott DC, Sehgal PB. Anti-beta-interferon antibodies inhibit the increased expression of HLA-B7 mRNA in tumor necrosis factor-treated human fibroblasts: structural studies of the beta 2 interferon involved. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8957–8961. [PMC free article] [PubMed]
  • Vaquero C, Sanceau J, Weissenbach J, Beranger F, Falcoff R. Regulation of human gamma-interferon and beta-interferon gene expression in PHA-activated lymphocytes. J Interferon Res. 1986 Apr;6(2):161–170. [PubMed]
  • Zilberstein A, Ruggieri R, Korn JH, Revel M. Structure and expression of cDNA and genes for human interferon-beta-2, a distinct species inducible by growth-stimulatory cytokines. EMBO J. 1986 Oct;5(10):2529–2537. [PMC free article] [PubMed]
  • Haegeman G, Content J, Volckaert G, Derynck R, Tavernier J, Fiers W. Structural analysis of the sequence coding for an inducible 26-kDa protein in human fibroblasts. Eur J Biochem. 1986 Sep 15;159(3):625–632. [PubMed]
  • Van Damme J, Cayphas S, Opdenakker G, Billiau A, Van Snick J. Interleukin 1 and poly(rI).poly(rC) induce production of a hybridoma growth factor by human fibroblasts. Eur J Immunol. 1987 Jan;17(1):1–7. [PubMed]
  • Van Damme J, Opdenakker G, Simpson RJ, Rubira MR, Cayphas S, Vink A, Billiau A, Van Snick J. Identification of the human 26-kD protein, interferon beta 2 (IFN-beta 2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor. J Exp Med. 1987 Mar 1;165(3):914–919. [PMC free article] [PubMed]
  • Content J, De Wit L, Poupart P, Opdenakker G, Van Damme J, Billiau A. Induction of a 26-kDa-protein mRNA in human cells treated with an interleukin-1-related, leukocyte-derived factor. Eur J Biochem. 1985 Oct 15;152(2):253–257. [PubMed]
  • Kohase M, Henriksen-DeStefano D, May LT, Vilcek J, Sehgal PB. Induction of beta 2-interferon by tumor necrosis factor: a homeostatic mechanism in the control of cell proliferation. Cell. 1986 Jun 6;45(5):659–666. [PubMed]
  • Kohase M, May LT, Tamm I, Vilcek J, Sehgal PB. A cytokine network in human diploid fibroblasts: interactions of beta-interferons, tumor necrosis factor, platelet-derived growth factor, and interleukin-1. Mol Cell Biol. 1987 Jan;7(1):273–280. [PMC free article] [PubMed]
  • Woloski BM, Smith EM, Meyer WJ, 3rd, Fuller GM, Blalock JE. Corticotropin-releasing activity of monokines. Science. 1985 Nov 29;230(4729):1035–1037. [PubMed]
  • Sehgal PB, Sagar AD. Heterogeneity of poly(I) x poly(C)-induced human fibroblast interferon mRNA species. Nature. 1980 Nov 6;288(5786):95–97. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...