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Biomedical subjects

L T May

Publications and source records attributed to L T May.

At least 37 records · Page 2Linked to original sources
PubMed1989

Cytokine-induced production of IFN-beta 2/IL-6 by freshly explanted human endometrial stromal cells. Modulation by estradiol-17 beta.

The cytokine IFN-beta 2/IL-6 has emerged as an important means of communication between cells--both within the immune system as well as outside it. In exploring the link between the endocrine and the immune systems, we have studied the secretion of IFN-beta 2/IL-6 by freshly explanted human endometrial stromal cells and its modulation by estrogens. Endometrial stromal cells produced IFN-beta 2/IL-6 in response to other inflammation-associated cytokines such as IL-1 alpha or beta, TNF, and IFN-gamma. This secretion was strongly inhibited by estradiol-17 beta at concentrations as low as 10(-9) M. Multiple species of stromal cell IFN-beta 2/IL-6 in the size range 23 to 30 kDa were detected using immunoprecipitation or immunoblotting procedures. The endometrial stromal cell IFN-beta 2/IL-6 species were phosphorylated and differentially glycosylated in a manner comparable to IFN-beta 2/IL-6 secreted by induced human peripheral blood monocytes or foreskin fibroblasts. However, in contrast to peripheral blood monocytes and fibroblasts, bacterial LPS did not induce IFN-beta 2/IL-6 production in endometrial stromal cells. Additionally, the IFN-beta 2/IL-6 identified in medium from IL-1 alpha-induced stromal cells is biologically active on hepatocytes. These observations, taken together with the observation that IFN-beta 2/IL-6 strongly inhibits the proliferation of human epithelial cells, suggest the possibility that stromal cell secreted IFN-beta 2/IL-6 may affect the physiology of the overlying epithelium in an hormonally modulated manner. Estrogen-regulated production of endometrial IFN-beta 2/IL-6 may participate in gender-specific systemic immunomodulation.

Adult↗
PubMed1989

Endotoxemia elicits increased circulating beta 2-IFN/IL-6 in man.

beta 2-IFN/hepatocyte stimulating factor/IL-6 is a cytokine secreted by monocytes, fibroblasts, and endothelial cells in cell culture that possesses diverse biologic activity including the stimulation of acute phase plasma protein synthesis and immunomodulation. The circulating levels of this cytokine in man in response to bacterial LPS (endotoxin) were studied. A single i.v. bolus of endotoxin (20 U/kg) produced a monophasic rise in circulating immunoreactive IFN-beta 2/IL-6 and IFN-beta 2/IL-6 bioactivity (hepatocyte stimulation and B cell differentiation assays) peaking 2 to 4 h after the endotoxin challenge. Peak IFN-beta 2/IL-6 levels ranged from 4.1 to 27.5 ng/ml. Associated with this was a rise in circulating C-reactive protein levels detected 20 h after the endotoxin bolus. Thus, IFN-beta 2/IL-6 is likely one of the endogenous mediators which is triggered in man during bacterial infection and likely participates in the metabolic and immune responses of the infected host.

Adult↗
PubMed1989

Interleukin-6 gene expression in human endothelial cells: RNA start sites, multiple IL-6 proteins and inhibition of proliferation.

Interleukin-6 (IL-6) is a cytokine which is not only produced by a wide variety of different cells but one which also affects the function of diverse tissues. We have studied the expression of the IL-6 gene in freshly explanted human umbilical vein endothelial cells (HUVEC) and have also evaluated the effect of IL-6 on HUVEC proliferation. Cytokines like interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor (TNF) as well as bacterial products such as the lipopolysaccharide (LPS) rapidly enhance production of biologically active IL-6 by HUVEC (IL-6 bioassay: increase in alpha 1-antichymotrypsin secretion by Hep3B2 cells and its neutralization by antiserum to E. coli-derived human IL-6). The two inducible RNA start sites in the IL-6 gene that are used in cytokine-induced fibroblasts (at +1 and -21) are also used in the same relative proportion (+1 greater than -21) in cytokine or LPS-induced HUVEC as determined by S1-nuclease protection assays for IL-6 transcripts. Immunoaffinity chromatography followed by Western blotting shows that IL-6 species secreted by IL-1 alpha-induced HUVEC are of molecular mass 23-25, 27-30 and 45 kDa as judged by SDS-PAGE under reducing conditions. Finally, rIL-6 inhibits [3H]-thymidine incorporation by HUVEC in a dose-dependent manner. Thus IL-6 is not only produced by HUVEC but may also affect its proliferation. The ability of the vascular endothelium to rapidly secrete IL-6 in response to inflammation-associated cytokines is of strategic value since it generates a circulatory signal which helps mobilize the acute phase plasma protein response and enlists the immune system in host defence.

Cell Line↗
PubMed1989

IL-6/IFN-beta-2 as a circulating hormone. Induction by cytokine administration in humans.

IL-6/IFN-beta 2 is a family of phosphoglycoproteins ranging in size from 19 to 30 kDa which elicits a broad range of physiologic and immune responses. Several cytokines, including TNF, have been shown to stimulate IL-6 production in cell culture. In this report, we describe the rapid induction of circulating biologically active IL-6 by the systemic administration of rTNF to patients with cancer. Low levels of IL-6 activity could be detected in the sera of patients as early as 5 min after rTNF infusion. IL-6 levels peaked approximately 2 to 3 h after rTNF bolus administration and were undetectable in most cases within 8 h. IL-6 was detected in two separate bioassays--the hybridoma B9 proliferation and the hepatocyte-stimulating factor assay. Maximum detectable levels of IL-6 ranged from 160 to 310 hybridoma growth factor units and 11-82 ng/ml in the hepatocyte-stimulating factor assay. IL-6 induction decreased after serial, daily doses of rTNF. Serial serum samples of patients receiving IL-2 or IFN-alpha were also assayed for IL-6 production. IL-2-treated but not IFN-alpha-treated patients generated low levels of IL-6 (range less than 20 to 95 hybridoma growth factor units/ml). Interestingly, in patients treated with IL-2, serum levels of TNF were detectable and peak TNF activity preceded measurable IL-6 levels. Serum levels of acute phase plasma proteins and of corticosteroid rose in response to rTNF administration. C-reactive protein increased (2.5 to 4.0-fold) within 8 h of rTNF administration and cortisol levels rose (10- to 20-fold) within 4 h after rTNF injection. We conclude that rTNF administration in man leads to the induction of circulating IL-6 which, due to its broad range of activities, may be an important physiologic signal regulating the immune response.

C-Reactive Protein↗
PubMed1989

Multiple forms of IFN-beta 2/IL-6 in serum and body fluids during acute bacterial infection.

Many of the major alterations in plasma proteins characteristic of the hepatic acute phase response are regulated by IFN-beta 2/IL-6. Using a specific bioassay for IFN-beta 2/IL-6, which relies on the induction of the hepatic acute phase plasma protein alpha 1-antichymotrypsin in the human hepatoma cell line Hep3B clone 2 and its inhibition by anti-rIFN-beta 2/IL-6 antiserum, we have detected high levels of IFN-beta 2/IL-6 in the body fluids of patients with acute bacterial infections. Cerebrospinal fluid from four patients with acute bacterial meningitis (Streptococcus pneumoniae, Staphylococcus aureus, two cases of Listeria monocytogenes) all had high levels of IFN-beta 2/IL-6 (up to 500 ng/ml). Two of these patients with concomitant bacteremia had lower concentrations of IFN-beta 2/IL-6 in the serum (5 to 70 ng/ml). Three additional patients with Escherichia coli, Pseudomonas aeruginosa, and Neisseria meningitidis bacteremia had high levels of serum IFN-beta 2/IL-6, as did the ankle fluid of a patient with Streptococcus canis arthritis. Normal cerebrospinal fluid and serum had little detectable IFN-beta 2/IL-6. A combination of immunoaffinity chromatography and immunoblotting procedures were used to characterize the IFN-beta 2/IL-6 species present in a representative sampling of serum and cerebrospinal fluids. Multiple immunoreactive species of IFN-beta 2/IL-6 in the size range 23 to 30 kDa as well as immunoreactive complexes in the range 60 to 70 kDa were detected in human body fluids. This is the first demonstration that previous descriptions of heterogeneity in human IFN-beta 2/IL-6 species produced in cell culture correspond to observations in the infected host.

Acute Disease↗
PubMed1989

A synergistic interaction of IL-6 and IL-1 mediates the thymocyte-stimulating activity produced by recombinant IL-1-stimulated fibroblasts.

We characterized the ability of normal human lung fibroblasts to elaborate thymocyte-stimulating activity, spontaneously, and in response to rIL-1. Supernatants from unstimulated fibroblasts did not contain thymocyte-stimulating activity, whereas supernatants from fibroblasts incubated with rIL-1 alpha or rIL-1 beta contained more thymocyte-stimulating activity than could be accounted for by passively transferred rIL-1 alone. This heightened thymocyte-stimulating activity was mediated by fibroblast-derived IL-6 inasmuch as it was neutralized by anti-serum against human rIL-6, and rIL-1-stimulated fibroblasts to accumulate messenger RNA for IL-6 and produce soluble IL-6 protein. However, IL-6 alone could not account for the intensity of this effect because rIL-6 only weakly stimulated thymocyte proliferation. In addition, antisera against the rIL-1 moiety that was used to prepare the supernatant had different effects on supernatants that contained and did not contain active IL-6. In the presence of IL-6 these antisera caused a greater decrease in thymocyte-stimulating activity than could be accounted for by passively transferred rIL-1 alone. When the IL-6 was neutralized the remaining thymocyte-stimulating activity could be quantitatively accounted for and neutralized by antisera against the rIL-1 that was passively transferred. Furthermore, rIL-6 and rIL-1 (alpha or beta) synergized in stimulating thymocyte proliferation. Thus, rIL-1 stimulates fibroblasts to produce a thymocyte-stimulating activity that is largely mediated by a synergistic interaction of fibroblast-derived IL-6 and IL-1. These findings suggest that fibroblast production of IL-6 may mediate or amplify some of the tissue effects of IL-1. In addition they suggest that biologic effects previously attributed to IL-1 may be due to IL-6 alone or the concerted action of IL-1 and IL-6.

Adult↗
PubMed1989

Post-translational modifications of human interleukin-6.

We have previously reported that interleukin (IL)-6 secreted by human fibroblasts induced with either IL-1 or tumor necrosis factor (TNF) consists of at least six differentially modified phosphoglycoproteins of molecular mass 23-30 kDa: a triplet in the mass range from 23 to 25 kDa and another triplet in the range from 28 to 30 kDa. We now report that a combination of metabolic labeling, glycosidase digestion, and lectin chromatography experiments demonstrates that the 23- to 25-kDa species are O-glycosylated and that the 28- to 30-kDa species are both O- and N-glycosylated. Pulse-chase experiments reveal that newly synthesized IL-6 polypeptides rapidly enter two separate protein modification pathways: one leads to O-glycosylation and the other to both N- and O-glycosylation; polypeptides in both pathways are further modified (phosphorylation) prior to secretion. Although both pathways appear to be equally utilized in IL-1- or TNF-induced fibroblasts, the relative proportion of polypeptides proceeding through one or the other pathway can be experimentally modified. In the presence of tunicamycin, IL-6 is secreted exclusively in the O-glycosylated form, whereas in the presence of cycloheximide the pathway leading to both N- and O-glycosylation is dominant. The inclusion of monensin (1 microM) does not inhibit IL-6 secretion from fibroblasts even though it inhibits glycosylation. Combined immunoprecipitation, immunoblotting, and immunoaffinity chromatography experiments reveal additional IL-6 species with mobilities in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions corresponding to molecular masses 17-19 kDa and 45 kDa, suggesting that this cytokine undergoes further alterations. These observations highlight an aspect of IL-6 biosynthesis that appears to represent an excellent model system for studying the mechanisms regulating post-translational protein modifications in human cells and also suggest a basis for reconciling conflicting descriptions of IL-6 structure.

Cell Line↗
PubMed1989

Interleukin 6 is expressed in high levels in psoriatic skin and stimulates proliferation of cultured human keratinocytes.

Psoriasis is a common papulosquamous skin disease. The histopathology is characterized by epidermal hyperplasia and inflammation. Recent studies suggest that keratinocyte proliferation and inflammation in psoriasis are manifestations of the same underlying pathological process. Interleukin 6 (IL-6), a cytokine that is a major mediator of the host response to tissue injury and infection, is produced by both keratinocytes and leukocytes in culture. IL-6 expression was studied in psoriatic plaques by immunoperoxidase staining with two different polyclonal anti-recombinant IL-6 antisera and by in situ nucleic acid hybridization with IL-6 cRNA probes. Epidermal and dermal cells in active psoriatic plaques from 35 psoriasis patients stained heavily for IL-6 as compared with nonlesional skin and with plaques after treatment with antimetabolic and antiinflammatory agents. Absorption of the anti-recombinant IL-6 antisera with purified fibroblast-derived IL-6 or with recombinant IL-6, but not bovine serum albumin, removed the immunostaining. Increased levels of IL-6 were detected in the plasma of patients with active psoriasis (mean 3 ng/ml) by using two different bioassays. IL-6 production by proliferating keratinocytes was suggested by IL-6-specific immunostaining in cultured normal and psoriatic keratinocytes and by the detection of mRNA specific for IL-6 in psoriatic epidermis by in situ hybridization. IL-6 stimulated the proliferation of cultured, normal human keratinocytes as assessed by two different assays. Thus, IL-6 could directly contribute to the epidermal hyperplasia seen in psoriatic epithelium as well as affect the function of dermal inflammatory cells.

Cell Division↗
PubMed1989

Interferon beta 2/interleukin 6 modulates synthesis of alpha 1-antitrypsin in human mononuclear phagocytes and in human hepatoma cells.

The cytokine IFN beta 2/IL-6 has recently been shown to regulate the expression of genes encoding hepatic acute phase plasma proteins. INF beta 2/IL-6 has also been shown to be identical to MGI-2, a protein that induces differentiation of bone marrow precursor cells toward mature granulocytes and monocytes. Accordingly, we have examined the effect of IFN beta 2/IL-6 on expression of the IL-1- and tumor necrosis factor-unresponsive acute phase protein alpha 1-antitrypsin (alpha 1 AT) in human hepatoma-derived hepatocytes and in human mononuclear phagocytes. Purified human fibroblast and recombinant IFN beta 2/IL-6 each mediate a specific increase in steady-state levels of alpha 1 AT mRNA and a corresponding increase in net synthesis of alpha 1 AT in primary cultures of human peripheral blood monocytes as well as in HepG2 and Hep3B cells. Thus, the effect of IFN beta 2/IL-6 on alpha 1 AT gene expression in these cells is primarily due to an increase in accumulation of alpha 1 AT mRNA and can be distinguished from the direct, predominantly translational effect of bacterial lipopolysaccharide on expression of this gene in monocytes and macrophages. The results indicate that IFN beta 2/IL-6 regulates acute phase gene expression, specifically alpha 1 AT gene expression, in extrahepatic as well as hepatic cell types.

Carcinoma, Hepatocellular↗
PubMed1989

Interleukin-6 immunoreactivity in human tumors.

The cytokine, interleukin-6 (IL-6), has emerged as a likely mediator of many of the systemic alterations observed in patients with cancer (fever, increased erythrocyte sedimentation rate, and alterations in plasma protein composition) and may also mediate local effects such as alteration in proliferation of tumor cells, increased tumor cell motility, and decreased intercellular adhesions between tumor cells. The distribution of IL-6 immunoreactivity in different human tumors was studied. IL-6 immunoreactivity was detected by the avidin-biotin-complex (ABC) procedure using a polyclonal rabbit antiserum raised against an E coli-derived human IL-6 (rIL-6). Preimmune rabbit serum used as a control did not yield specific staining and preadsorption of the IL-6 antiserum with rIL-6 abolished specific staining. Strong-to-moderate IL-6 immunoreactivity was observed in the neoplastic elements present in primary squamous cell carcinomas, in adenocarcinomas of mammary, colonic, ovarian, and endometrial origin, in various adenocarcinomas metastatic to lymph nodes, and in soft tissue tumors including leiomyosarcoma and neurofibrosarcoma. Weak-to-moderate IL-6 immunostaining was observed in Hodgkin's and non-Hodgkin's lymphomas. This study demonstrates that most human tumors stain positively for IL-6, adding weight to the hypothesis that IL-6 is a key cytokine that participates in the host-tumor interaction.

Cell Line↗
PubMed1988

Synthesis and secretion of multiple forms of beta 2-interferon/B-cell differentiation factor 2/hepatocyte-stimulating factor by human fibroblasts and monocytes.

The cDNA for human beta 2-interferon (IFN-beta 2)/B-cell differentiation factor 2/hepatocyte-stimulating factor was expressed in Escherichia coli to yield a fusion protein which contains the 182 carboxyl-terminal amino acids of IFN-beta 2 fused to a 34-amino acid prokaryotic leader peptide (rIFN-beta 2). When added to cultures of human hepatoma cell line Hep3B2, rIFN-beta 2 as well as preparations of natural IFN-beta 2 enhance secretion of positive acute phase reactants such as alpha 1-antichymotrypsin, complement C3, fibrinogen, and alpha 1-acid glycoprotein and inhibit secretion of albumin, confirming that a protein derived from the IFN-beta 2 gene can have hepatocyte-stimulating factor activity. We have prepared a rabbit polyclonal antiserum to the E. coli-derived human IFN-beta 2 fusion protein. This polyclonal antiserum inhibits the hepatocyte-stimulating and B-cell differentiation activities of appropriate IFN-beta 2 preparations. The anti-rIFN-beta 2 antiserum has been used in immunoprecipitation experiments and in Western blots to help define the secretory proteins derived from the IFN-beta 2 gene in fibroblasts and monocytes. "Uninduced" human FS-4 fibroblasts as well as those induced with interleukin-1 alpha, tumor necrosis factor, or bacterial lipopolysaccharide secrete at least five forms of IFN-beta 2 of apparent molecular mass in the range from 23 to 30 kDa which can be resolved by polyacrylamide gel electrophoresis under denaturing and reducing conditions. The three higher molecular mass forms are not observed when FS-4 cells are induced in the presence of tunicamycin, suggesting that these forms are N-glycosylated (gp28, gp29, and gp30). Although secretion of the two lower molecular mass forms is resistant to tunicamycin, they are labeled by [3H]glucosamine (gp23-gp25). The inclusion of cycloheximide during the [35S]methionine labeling of induced FS-4 cells results in the preferential synthesis and secretion of the 29-kDa triplet. Human monocytes induced with bacterial lipopolysaccharide also secrete several distinct forms of IFN-beta 2 in the size range from 23 to 30 kDa which co-migrate in polyacrylamide gels with those obtained from FS-4 cells. Our observations help relate previous descriptions of multiple forms of hepatocyte-stimulating factor to specific proteins derived from the IFN-beta 2 gene.

Animals↗
PubMed1988

Regulation of the acute phase and immune responses in viral disease. Enhanced expression of the beta 2-interferon/hepatocyte-stimulating factor/interleukin 6 gene in virus-infected human fibroblasts.

We have defined the expression of the mRNA for, and secretion of, IFN-beta 2/hepatocyte-stimulating factor/IL-6 (IFN-beta 2/IL-6) in human diploid fibroblasts (FS-4 strain) infected with different RNA- and DNA-containing viruses. RNA blot-hybridization analyses carried out 6-8 h after the beginning of infection showed that the RNA-containing Sendai virus (paramyxoviridae) enhanced IFN-beta 2/IL-6 mRNA levels 10-fold, followed, in decreasing order, by encephalomyocarditis (EMC, picornaviridae), vesicular stomatitis (VSV, rhabdoviridae), Newcastle disease virus (NDV, paramyxoviridae), and influenza A (Flu, myxoviridae) viruses. The DNA-containing pseudorabies virus (PR, herpesviridae) enhanced IFN-beta 2/IL-6 mRNA levels sixfold, while the effect of adenovirus type 5 (Ad5, adenoviridae) was considerably less and comparable with that of NDV or Flu. A rabbit antiserum raised against E. coli-derived human IFN-beta 2/IL-6 was used in immunoprecipitation experiments to monitor the secretion of 35S-methionine-pulse-labeled IFN-beta 2/IL-6 proteins by fibroblasts up to 7 h after the beginning of infection. Enhanced levels of secretion of IFN-beta 2/IL-6 (2-14-fold) were observed in every instance evaluated (Sendai, EMC, VSV, Flu, PR, Ad5 viruses). A biological consequence of enhanced secretion of IFN-beta 2/IL-6 was the ability of media from infected FS-4 cell cultures to enhance by 8-15-fold the synthesis and secretion of a typical acute phase plasma protein (alpha 1-antichymotrypsin) by human hepatoma Hep3B2 cells. These observations make it likely that IFN-beta 2/IL-6 mediates, in part, the host response to acute virus infections.

Acute-Phase Reaction↗
PubMed1988

Phosphorylation of secreted forms of human beta 2-interferon/hepatocyte stimulating factor/interleukin-6.

"Beta 2-Interferon/hepatocyte stimulating factor/interleukin-6" (IFN-beta 2) has emerged as a major mediator of the plasma protein response to tissue injury (the acute phase response) in addition to its numerous effects on cells of the immune system. Human fibroblasts and monocytes induced with tumor necrosis factor, interleukin-1, bacterial lipopolysaccharide (endotoxin) or virus infection secrete multiple forms of differentially glycosylated IFN-beta 2 polypeptides: at least a doublet of molecular mass approximately 25 kD and a triplet of mass approximately 30 kD. We report that immunoprecipitation analyses of medium from [32P]orthophosphate- labeled cultures of induced fibroblasts carried out using a rabbit polyclonal antibody to recombinant E. coli-derived human IFN-beta 2 reveal that the secreted gp23-25 and gp28-30 forms of IFN-beta 2 are phosphorylated. IFN-beta 2 gp23-25 secreted by induced monocytes is phosphorylated whereas the monocytic gp28-30 is poorly labeled with [32P]orthophosphate suggesting tissue-specific differences in IFN-beta 2 phosphorylation. Phosphoamino acid analyses indicate that all of the detected phosphate is in phosphoserine residues. Furthermore, IFN-beta 2 can be completely dephosphorylated by alkaline phosphatase (E.C. No. 3.1.3.1); thus all of the phosphate label is in readily accessible sites. These observations suggest the possibility that differential phosphorylation of IFN-beta 2 forms may be a mechanism to modulate its functions in a tissue-specific manner.

Alkaline Phosphatase↗
PubMed1988

Transcriptional regulation of the interferon-beta 2/B cell differentiation factor BSF-2/hepatocyte-stimulating factor gene in human fibroblasts by other cytokines.

Levels of mRNA for IFN-beta 2/B cell differentiation factor2/hepatocyte-stimulating factor (IFN-beta 2) in confluent quiescent cultures of human diploid fibroblasts (FS-4 strain) are enhanced by TNF, IL-1 alpha and beta, platelet-derived growth factor (PDGF) and IFN-beta 1. Of these cytokines, IL-1 alpha and beta cause a particularly strong increase in the accumulation of IFN-beta 2 mRNA in fibroblasts. We have evaluated whether the IFN-beta 2 gene is regulated at the transcriptional level by using nuclear run-on transcription assays. We observed that the IFN-beta 2 gene is transcribed at a low level in uninduced FS-4 cells and that this transcriptional activity is increased 2- to 3-fold in cycloheximide-treated cells, 20- to 35-fold in IL-1 alpha-treated cells, and 5- to 15-fold in TNF-treated cells. PDGF and IFN-beta 1 enhance transcription across the IFN-beta 2 gene 2- to 3-fold. The enhancing effect of IL-1 alpha on IFN-beta 2 gene transcription, but not that of TNF, PDGF, or IFN-beta 1, is inhibited by cycloheximide, suggesting that newly-synthesized protein is involved in the increase in IFN-beta 2 transcription in response to IL-1 alpha but not in the response to the other stimuli. Furthermore, the enhancement of IFN-beta 2 transcription is sustained for up to 14 h after IL-1 alpha induction but is transient and declines to base line levels within 6 h after TNF addition. These observations suggest that there are important differences in the mechanisms by which IL-1 alpha and TNF increase IFN-beta 2 gene transcription in fibroblasts.

Base Sequence↗
PubMed1988

Monocyte-derived human B-cell growth factor identified as interferon-beta 2 (BSF-2, IL-6).

Soluble products of either Epstein-Barr virus (EBV)-infected B cells or activated monocytes promote the proliferation of EBV-infected B cells and permit their growth at low cell densities. This suggests that growth factors are important for B-cell immortalization by EBV. In this study, a monocyte-derived factor that promotes the growth of EBV-infected b cells was purified and identified as interferon-beta 2 (IFN-beta 2), which is also known as 26-kilodalton protein, B-cell differentiation factor (BSF-2), and interleukin-6 (IL-6). The purified protein has a specific activity of approximately 4 X 10(7) units per milligram of protein in assays of B-cell growth. Thus, IFN-beta 2/BSF-2 is a B-cell growth factor that promotes the proliferation of human B cells infected with EBV.

B-Lymphocytes↗