Cytokine Yearbook Volume 1: An Official Publication of the International Society for Interferon and Cytokine Research

99 Pages·5.258 MB·English

by  Filippo Belordelli (auth.), S. Pestka, H. Schellekens, P. Von Wussow (eds.)

CYTOKINE YEARBOOK
Cytokine Yearbook
Volume 1
An Official Publication of the
International Society for Interferon and Cytokine Research
Edited by
S.PESTKA
New Jersey's University of the Health Sciences,
Piscataway, NJ, USA
H. SCHELLEKENS
Diagnostisch Centrum SSDZ, Delft, The Netherlands
and
P. VON WUSSOW
Medizinische Hochschule Hannover, Hannover, Germany
Reprinted from Biotherapy, Volume 8, Nos. 3-4 (1996)
KLUWER ACADEMIC PUBLISHERS
DORDRECHT I BOSTON I LONDON
A C.I.P. Catalogue record for this book is available from
the Library of Congress.
ISBN-13:978-94-010-7221-2 e-ISBN-13:978-94-009-1616·6
DOl: 10.10071978-94-009-1616-6
ISSN 1384-1238
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© 1996 Kluwer Academic Publishers
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Table of contents
Preface Ix
In memoriam Prof. Giovanni Rossi 153-155
F. Belardelli
Type I Interferon genes and proteins 157-162
M.O. Dlaz & D. Testa
Interferon receptors 163-174
J. Langer, G. Garotta & S. Pestka
Interferon signal transduction 175-181
A. Lamer & N.C. Reich
Induction of Interferons and Interferon-induced genes 183-187
C.E. Samuel & K. Ozato
Biological effects of the Interferons and other cytoklnes 189-198
R.M. Friedman, P. Grimley & S. Baron
Factors Inhibiting IFN activity 199-204
H. Schellekens, P.H. van der Meide & P. von Wussow
Oral application of cytoklnes 205-212
J.A. Georgiades & W.R. Fleischmann, Jr.
Interferons and the tumor cell 213-218
H. Strander & S. Einhorn
Cytoklnes and bacterial Infections 219-228
M.Degre
Cytoklnes In animal models of cancer 229-241
F. Burke & F.R. Balkwill
Cytoklnes and the Immune response 243-249
P.H. Van der Meide & H. Schellekens
Dedicated to the late Dr. Rossi -
a valued friend, teacher & colleague.
Biotherapy 8: ix, 1996. ix
II:) 1996 Kluwer Academic Publishers.
Preface
This special issue of Biotherapy which will also appear as the 1995 Cytokine Yearbook is an experiment. It is a
hybrid between an update on the recent developments in cytokine research and a meeting report. We have invited a
number of distinguished colleagues who are experts in their specific fields to review their areas of interest by using
the presentations and discussions at the 1994 international meeting of the International Society for Interferon and
Cytokine Research (ISICR) as the basis.
This yearbook has been acknowledged by the Publications Committee as an ISICR publication. In the future
we will also try to include the annual meeting of the International Cytokine Society to broaden the base of this
yearbook. The first combined annual meeting of the ISICR and ICS will be organised in 1996 in Geneva, which
provides an excellent opportunity for such a comprehensive effort.
We have not intended to cover the whole field, but we have selected a number of themes. The intention is to
pay attention to other topics in the years to come. The authors were not obliged to restrict themselves to what was
presented and discussed at the ISICR meeting in Budapest. They could also include their own or others, published
and unpublished data. The result is an interesting collection of overviews.
The scientific level of the contributions is high, but their format differs as a consequence of the experimental
character of this first yearbook. Based on the reactions of the readers a more universal format will be chosen for the
future volumes. So please send your comments to the editors and also contact them if you want to suggest topics
or possible contributors or even better, if you want to contribute to the next volumes yourself.
The Editors
Biotherapy 8: 153-155, 1996. 153
© 1996 Kluwer Academic Publishers.
In memoriam Prof. Giovanni Rossi
Giovanni B. Rossi died on February 20 1994, at the Giovanni Rossi made major contributions to the
age of only 58, after an intense struggle with a non interferon field over the years. From the moment he
Hodgkin's lymphoma diagnosed over 9 years ago. graduated in medicine and surgery in 1959,Giovanni
Most of you knew him very well because of his work dedicated himself to virus and cancer research. From
in the interferon field. He regularly attended our inter 1965 to 1969, he worked on the biology of mouse
feron meetings since the very beginning. However, erythroleukemia cells in New York, in the Laboratory
until recently, only a few close friends knew about his of Charlotte Friend, who had discovered the Friend
serious illness as Giovanni never exhibited his illness. Virus a few years before. During those years, Giovan
He managed not only to carry on his usual work as ni published several important articles on the biology
effective as ever, but also committed himself to new of the Friend Virus. This period had a fundamental
and more demanding projects such as the organization, influence on his future research interests in interfer
together with Prof Ferdinando Dianzani, of the 1989 on. Remembering those years spent working together
interferon meeting held in Florence and two years later, with Charlotte Friend, Giovanni wrote: "In the 60's,
the organization of the International AIDS Conference, when I had the privilege of meeting and working with
also held in Florence. C. Friend for three wonderful and fundamental years,
she was a lonely pioneer. ... She observed that neoplas-
154
tic cells did indeed differentiate. Under exposure to The work carried out on Friend cell clones, sen
DMSO, it appeared that events related to differentia sitive or resistant to interferon alpha, beta or gamma,
tion of murine erythroid leukemic cells into orthochro showed tIlat these cells express high affinity recep
matic erythroblasts would override the mechanisms tors for interferon-a1phalbeta or gamma similarly to
leading leukemic cells into indefinite self-renewal. A interferon-sensitive parental cells. The lack of induc
2-log difference was observed when DMSO-treated tion of the antiviral state and of the antiproliferative
leukemic cells were assayed for tumorigenicity in sus effects by interferon in these cells were proved to be
ceptible syngeneic mice. That experiment, though a associated with the lack of induction of interferon
bit naive, was one of the earliest to test differentiation specific genes. Thus, in the subsequent years, these
related inhibition of tumorigenicity" (in "The Status of clones turned out to be also useful in studies on signal
Differentiation Therapy of Cancer", Serono Symposia transduction.
Publications from Raven Press, New York, 1988). Giovanni's early interest in cell differentiation
These remarks, I think, reflect his enthusiastic interest remained one of his main interests. He fervently
in the differentiation of tumor cells, which was con believed in the possible application of iQese studies
stant over the years. As a matter of fact, his subsequent in the field of antitumor therapy, using the approach
research interests concentrated on the studies of effects of modulating the phenotype of tumor cells by dif
of different biological response modifiers, in particu ferentiating agents. He organized special meetings on
lar interferons, on the growth and differentiation of "Differentiation therapy of cancer" each year, togeth
tumor cells (especially Friend erythroleukemia cells). er with Drs. Samuel Waxman and Fumimaro Takaku.
In 1968, Giovanni set up his own research group at the These meetings brought together scientists working on
Istituto Superiore di Sanita in Rome (the major pub different aspects related to cell growth and differen
lic Health Institute in Italy), where he was appointed tiation in a workshop setting to define new strategies
Director of the Laboratory of Virology in 1982. Here, for the development of differentiation therapy of can
in the early '70s, he began to work on IFN. Giovan cer.
ni thought that the Friend virus transformed cell lines Giovanni deeply loved science and dedicated most
established in C. Friend's Laboratory could be a use of his time to interferon research. He considered him
ful tool to investigate the effects of interferon on cell self a lucky person as he had the privilege of dedicating
growth, differentiation and retrovirus expression. most of his time to research. As an example of his love
At a time when interferons were still considered, at for interferon research, I would like to quote these sen
least by the majority of the Scientific Community, as tences written in the acknowledgements at the end of a
simple antiviral substances, his major interest was to review on interferon and cell differentiation: "I am lov
evaluate the in vitro effects of interferons on multipli ingly indebted to my children for keeping me alert on
cation of Friend leukemia cells (FLC). His early publi the interferon issue by reiterating the question (mainly
cations on interferon dealt with the effects of interferon on Sundays which I spent at work): "Dad, are inter
on FLC, more specifically on: 1) cell growth, 2) dif ferons real or are they just your toy?" " (Interferon 6,
ferentiation and 3) retrovirus production. Academic Press, New York, 1985). As a matter of fact,
As a matter of fact, Friend erythroleukemia cells, interferon could be considered his 'toy', as interferon
and interferon-resistant clones isolated by Elisabetta research remained his best-loved activity, even though
Affabris in his Laboratory, turned out to be extreme he became involved in several new important activities
ly useful during the following years, not only for in over the following years. In particular, since the early
vitro studies on the mechanisms of action of interfer 80s, as Head of the Department of Virology at the ISS,
on (which were personally supervised by Giovanni in he immediately felt the responsibility for applying his
subsequent years), but also for in vivo studies on the efforts to the fight against AIDS and on understanding
host-mediated antitumor effects of interferon which the molecular mechanisms involved in the replication
were started when, following Giovanni's suggestion, and dissemination of HIV. In 1986, he became full
I spent one year (in 1981) in Ion Gresser's Laborato professor of Microbiology, but he chose to remain in
ry. Giovanni always encouraged me to continue our our Institute as Director of Research and Head of our
studies on the antitumor effects of interferon and other Department. He became the leader of the Italian AIDS
cytokines in mice and I am personally indebted to him project (funded by the Ministry of Health), which has
for all the work we developed over the years in our provided financial support for high quality research on
laboratories. AIDS in Italy for the last seven years. As pointed out
155
in a recent note published in Nature, Giovanni intro who knew him. As written in the obituary published
duced a new selection procedure in Italy, based on "a in the Journal of Interferon Research, signed by Drs.
strict international peer review system for grant appli Ferdinando Dianzani, Samuel Baron and Sidney Pest
cations, followed by published and detailed accounts ka, "his secret was never to give much importance
every year" (A. Abbott, Nature, February 1994). As to minor problems, such as blood transfusions and
a matter of fact, the high level of integrity reflected treatments that might have prevented him from attend
in all his work was generally recognized by the Sci ing a meeting, chairing a conference, or discussing a
entific Community. He was also the Project Leader of project". He was awarded several honors in recogni
a Special Concerted Action on HIY variability sup tion of his work. Yet, perhaps most notable was the
ported by the European Community. In the last years, admiration and affection felt by the staff of his Labora
much of his efforts were devoted to AIDS research. tory, his colleagues in the Institute and by the Scientific
But, much of his efforts were also devoted to the cre Community as a whole.
ation of new laboratory facilities for our Department, The field of interferon and cytokine research has
and especially, in the last few months, to the creation now lost one of its outstanding scientists. With great
of a new Primate Center capable of housing more than sadness, some of us have lost a unique and extraor
100 monkeys infected with SlY which, unfortunately, dinarily generous friend. However, I like the idea of
was activated only after his death. thinking that Giovanni Rossi will always be among us
In 1988, Giovanni wrote: "On January 13, 1987 as he remains not only an inspiration for new research
Charlotte Friend died of a disease similar to that which projects on interferon and cytokines, but also a dai
she studied throughout her professional life. Her strug ly example to young scientists on how to combine a
gle lasted long always endowed with dignity, relentless strong love for science with important personal qual
work, and lack of self-pity. Ifp sychological defiance of ities rarely associated in one person such as critical
neoplasia could bear a lively fruit, she would have been insight, generosity and great courage.
spared death" ("The Status of Differentiation Therapy Lastly, on behalf of many Italian scientists and
of Cancer", Serono Symposia Publications from Raven colleagues who had the privilege of knowing Gio
Press, New York, 1988). I think it is peculiar that what vanni and working with him, I would like to
he wrote for C. Friend could be easily, now, said about end by saying, once again: "Grazie, Giovanni".
Giovanni's life. In the last few years, Giovanni's illness
began to progress in spite of all the treatments, but up Filippo Belordelli
tothe end his outstanding courage impressed everyone
Biolherapy 8: 157-162, 1996. 157
© 1996 Kluwer Academic Publishers.
Type I interferon genes and proteins
Manuel O. Diaz1 & Douglas Testa2
1L oyola University Cancer Center; 2160 South First Avenue, Maywood, Illinois 60153, USA; 2A AG incorporated,
PO Box 6, Phillipsburg, New Jersey 08865, USA
Key words: interferon, gene expression, interferon receptor, interferon evolution, genomic mapping
Abstract
The large number of type I interferon genes in mammalian species could be explained by simple redundancy, by
different functions for different interferons, or by different spatial or temporal patterns of expression. Different
functions would require different receptors for each interferon, while different patterns of expression would require
different transcriptional or postranscriptional regulatory mechanisms. It is also necessary to explain when and
how this diversity was achieved. Information on comparative genetics of the interferon system, cloning of new
interferon genes, studies on receptor interactions and studies on gene expression are accrued at each of the annual
meetings of the ISICR. The last meeting held on October 2-7, 1994, at Budapest was not an exception, and this
review summarizes some of this year's reports.
Introduction tant to understand which selective forces drove this
expansion, and how the different interferohs relate to
The large number and diversity of type I interferon the range of pathogens to which the different species
genes in mammalian species still puzzles investiga have been exposed, and to the evolution ofn ew repro
tors in this field. This diversity of the type I interferon ductive mechanisms, like placentation.
genes in mammals, cannot be explained only as genetic
redundancy. We are still searching for different func
tions, different receptors or different interactions with Avian interferons
the same receptor, and for differential spatial or tem
poral patterns of gene expression, that could explain The chicken interferon gene was cloned as a cDNA
such diversity. The study of the interferon system in that codes for a protein of 193 amino acids, including a
different mammalian species has revealed new aspects 31 amino acid signal peptide [25, 26] At the aminoacid
of this diversity in the multiple 1FN-f3 genes of the level, the highest similarity is with lPN-a and IPN-w of
bovines [31], and the 1FN-r [22, 23] of the ruminants. mammals (24%). Unlike the human type I interferons
In this meeting, reports on the cloning and character which have only a single putative glycosylation site
ization of two type I avian interferons were added to and three or four cysteines per molecule, the chicken
the family. interferon has four potential N-glycosylation sites and
The time in evolution at which this diversity devel six cysteines. Protein produced in COS-7 cells trans
oped and the mechanism for expansion and divergence fected with an expression vector for this gene, shows
of the interferon genes in mammals are also fascinat biological activity on chicken cells, inducing the Mx
ing subjects. So far only the genomic organization of promoter. Data from Southern blot hybridization sug
the human type I interferon genes is known in detail, gests that there is a single gene of this family in the
but the apparent simplicity of the avian interferon sys chicken genome.
tem suggests that expansion occurred during the mam Using the chicken interferon cDNA as a probe,
malian evolutionary radiation. It would also be impor- Schultz et al. [24], cloned a duck genomic DNA frag-