Human cytokines, tumor necrosis factor, and interferons: Gene cloning, animal studies, and clinical trials

Arthur P. Bollon, Susan L. Berent, Richard M. Torczynski, Norwood O. Hill, Yuri Lemeshev, Joseph M. Hill, Feng Lan Jia, Anwar Joher, Sathit Pichyangkul, Amanullah Khan

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Presented is a comprehensive program designed to isolate human cytokine genes and investigate their relative induction, and to analyze cytokine activities in cell culture, animal tumor models, and human clinical trials. Human cytokine cDNAs have been isolated from a cDNA library made from normal human peripheral blood leukocytes (PBLs) treated with Sendai virus and the relative induction of tumor necrosis factor (TNF), alpha and gamma interferons (IFN‐α, IFN‐γ), and interleukin‐1 beta IL‐1β genes has been analyzed. In the Sendai virus‐induced PBL system, IL‐1β mRNA was shown to be approximately twofold higher than TNF or IFN‐α mRNA whereas IFN‐γ mRNA was 50–100‐fold lower than TNF or IFN‐α mRNA. The cytotoxic activity of TNF was analyzed on several cell lines and IFN‐α and IFN‐γ were shown to potentiate TNF cytotoxicity about 2–200‐fold depending on cell lines. The LD50 for recombinant TNF in BALB/c mice was determined to be 6 × 107 U/kg and the therapeutic dose of recombinant TNF in sarcoma 180 bearing BALB/c mice was 3 × 105 U/kg, indicating a wide therapeutic index. Phase I clinical trials of recombinant TNF given I.V. indicated a tolerated dose of 150,000 U/kg with biphasic half‐life (T‐1/2) of 2 and 31 min following TNF injection. Phase II trials of TNF and trials of TNF combined with IFN‐α are in progress. These studies indicate that cytokines such as TNF and IFN‐α are subject to similar induction systems, potentiate each other's activities, and can be tolerated at specific doses for potential therapeutic use.

Original languageEnglish (US)
Pages (from-to)353-367
Number of pages15
JournalJournal of Cellular Biochemistry
Volume36
Issue number4
DOIs
StatePublished - 1988

Fingerprint

Cloning
Interferons
Organism Cloning
Animals
Tumor Necrosis Factor-alpha
Genes
Clinical Trials
Cytokines
Messenger RNA
human TNF protein
Animal cell culture
Leukocytes
Blood
Bearings (structural)
Cells
Sarcoma 180
Sendai virus
Virus Activation
Cell Line
Clinical Trials, Phase I

Keywords

  • clinical use
  • genes
  • IFN
  • TNF

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Bollon, A. P., Berent, S. L., Torczynski, R. M., Hill, N. O., Lemeshev, Y., Hill, J. M., ... Khan, A. (1988). Human cytokines, tumor necrosis factor, and interferons: Gene cloning, animal studies, and clinical trials. Journal of Cellular Biochemistry, 36(4), 353-367. https://doi.org/10.1002/jcb.240360405

Human cytokines, tumor necrosis factor, and interferons : Gene cloning, animal studies, and clinical trials. / Bollon, Arthur P.; Berent, Susan L.; Torczynski, Richard M.; Hill, Norwood O.; Lemeshev, Yuri; Hill, Joseph M.; Jia, Feng Lan; Joher, Anwar; Pichyangkul, Sathit; Khan, Amanullah.

In: Journal of Cellular Biochemistry, Vol. 36, No. 4, 1988, p. 353-367.

Research output: Contribution to journalArticle

Bollon, AP, Berent, SL, Torczynski, RM, Hill, NO, Lemeshev, Y, Hill, JM, Jia, FL, Joher, A, Pichyangkul, S & Khan, A 1988, 'Human cytokines, tumor necrosis factor, and interferons: Gene cloning, animal studies, and clinical trials', Journal of Cellular Biochemistry, vol. 36, no. 4, pp. 353-367. https://doi.org/10.1002/jcb.240360405
Bollon, Arthur P. ; Berent, Susan L. ; Torczynski, Richard M. ; Hill, Norwood O. ; Lemeshev, Yuri ; Hill, Joseph M. ; Jia, Feng Lan ; Joher, Anwar ; Pichyangkul, Sathit ; Khan, Amanullah. / Human cytokines, tumor necrosis factor, and interferons : Gene cloning, animal studies, and clinical trials. In: Journal of Cellular Biochemistry. 1988 ; Vol. 36, No. 4. pp. 353-367.
@article{44c0ca2cdc574972974536a1b30e2f75,
title = "Human cytokines, tumor necrosis factor, and interferons: Gene cloning, animal studies, and clinical trials",
abstract = "Presented is a comprehensive program designed to isolate human cytokine genes and investigate their relative induction, and to analyze cytokine activities in cell culture, animal tumor models, and human clinical trials. Human cytokine cDNAs have been isolated from a cDNA library made from normal human peripheral blood leukocytes (PBLs) treated with Sendai virus and the relative induction of tumor necrosis factor (TNF), alpha and gamma interferons (IFN‐α, IFN‐γ), and interleukin‐1 beta IL‐1β genes has been analyzed. In the Sendai virus‐induced PBL system, IL‐1β mRNA was shown to be approximately twofold higher than TNF or IFN‐α mRNA whereas IFN‐γ mRNA was 50–100‐fold lower than TNF or IFN‐α mRNA. The cytotoxic activity of TNF was analyzed on several cell lines and IFN‐α and IFN‐γ were shown to potentiate TNF cytotoxicity about 2–200‐fold depending on cell lines. The LD50 for recombinant TNF in BALB/c mice was determined to be 6 × 107 U/kg and the therapeutic dose of recombinant TNF in sarcoma 180 bearing BALB/c mice was 3 × 105 U/kg, indicating a wide therapeutic index. Phase I clinical trials of recombinant TNF given I.V. indicated a tolerated dose of 150,000 U/kg with biphasic half‐life (T‐1/2) of 2 and 31 min following TNF injection. Phase II trials of TNF and trials of TNF combined with IFN‐α are in progress. These studies indicate that cytokines such as TNF and IFN‐α are subject to similar induction systems, potentiate each other's activities, and can be tolerated at specific doses for potential therapeutic use.",
keywords = "clinical use, genes, IFN, TNF",
author = "Bollon, {Arthur P.} and Berent, {Susan L.} and Torczynski, {Richard M.} and Hill, {Norwood O.} and Yuri Lemeshev and Hill, {Joseph M.} and Jia, {Feng Lan} and Anwar Joher and Sathit Pichyangkul and Amanullah Khan",
year = "1988",
doi = "10.1002/jcb.240360405",
language = "English (US)",
volume = "36",
pages = "353--367",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Human cytokines, tumor necrosis factor, and interferons

T2 - Gene cloning, animal studies, and clinical trials

AU - Bollon, Arthur P.

AU - Berent, Susan L.

AU - Torczynski, Richard M.

AU - Hill, Norwood O.

AU - Lemeshev, Yuri

AU - Hill, Joseph M.

AU - Jia, Feng Lan

AU - Joher, Anwar

AU - Pichyangkul, Sathit

AU - Khan, Amanullah

PY - 1988

Y1 - 1988

N2 - Presented is a comprehensive program designed to isolate human cytokine genes and investigate their relative induction, and to analyze cytokine activities in cell culture, animal tumor models, and human clinical trials. Human cytokine cDNAs have been isolated from a cDNA library made from normal human peripheral blood leukocytes (PBLs) treated with Sendai virus and the relative induction of tumor necrosis factor (TNF), alpha and gamma interferons (IFN‐α, IFN‐γ), and interleukin‐1 beta IL‐1β genes has been analyzed. In the Sendai virus‐induced PBL system, IL‐1β mRNA was shown to be approximately twofold higher than TNF or IFN‐α mRNA whereas IFN‐γ mRNA was 50–100‐fold lower than TNF or IFN‐α mRNA. The cytotoxic activity of TNF was analyzed on several cell lines and IFN‐α and IFN‐γ were shown to potentiate TNF cytotoxicity about 2–200‐fold depending on cell lines. The LD50 for recombinant TNF in BALB/c mice was determined to be 6 × 107 U/kg and the therapeutic dose of recombinant TNF in sarcoma 180 bearing BALB/c mice was 3 × 105 U/kg, indicating a wide therapeutic index. Phase I clinical trials of recombinant TNF given I.V. indicated a tolerated dose of 150,000 U/kg with biphasic half‐life (T‐1/2) of 2 and 31 min following TNF injection. Phase II trials of TNF and trials of TNF combined with IFN‐α are in progress. These studies indicate that cytokines such as TNF and IFN‐α are subject to similar induction systems, potentiate each other's activities, and can be tolerated at specific doses for potential therapeutic use.

AB - Presented is a comprehensive program designed to isolate human cytokine genes and investigate their relative induction, and to analyze cytokine activities in cell culture, animal tumor models, and human clinical trials. Human cytokine cDNAs have been isolated from a cDNA library made from normal human peripheral blood leukocytes (PBLs) treated with Sendai virus and the relative induction of tumor necrosis factor (TNF), alpha and gamma interferons (IFN‐α, IFN‐γ), and interleukin‐1 beta IL‐1β genes has been analyzed. In the Sendai virus‐induced PBL system, IL‐1β mRNA was shown to be approximately twofold higher than TNF or IFN‐α mRNA whereas IFN‐γ mRNA was 50–100‐fold lower than TNF or IFN‐α mRNA. The cytotoxic activity of TNF was analyzed on several cell lines and IFN‐α and IFN‐γ were shown to potentiate TNF cytotoxicity about 2–200‐fold depending on cell lines. The LD50 for recombinant TNF in BALB/c mice was determined to be 6 × 107 U/kg and the therapeutic dose of recombinant TNF in sarcoma 180 bearing BALB/c mice was 3 × 105 U/kg, indicating a wide therapeutic index. Phase I clinical trials of recombinant TNF given I.V. indicated a tolerated dose of 150,000 U/kg with biphasic half‐life (T‐1/2) of 2 and 31 min following TNF injection. Phase II trials of TNF and trials of TNF combined with IFN‐α are in progress. These studies indicate that cytokines such as TNF and IFN‐α are subject to similar induction systems, potentiate each other's activities, and can be tolerated at specific doses for potential therapeutic use.

KW - clinical use

KW - genes

KW - IFN

KW - TNF

UR - http://www.scopus.com/inward/record.url?scp=0023897718&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023897718&partnerID=8YFLogxK

U2 - 10.1002/jcb.240360405

DO - 10.1002/jcb.240360405

M3 - Article

C2 - 2454238

AN - SCOPUS:0023897718

VL - 36

SP - 353

EP - 367

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 4

ER -