[Journal Article: Effect of Acetyl Salicylic Acid on Producation and Action of Leukocyte-Derived Interferons] Page: 1 of 4
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Vol. 31, No. 1
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Jan. 1987, p. 114-116
Copyright 1987, American Society for Microbiology
Effect of Acetyl Salicylic Acid on Production and Action of
SHOOKOOH YOUSEFI, JOSEPH CHIU, GLORIA CARANDANG, ERIC G. ARCHIBEQUE,
NOSTRATOLA VAZIRI, AND THOMAS C. CESARIO*
University of California Irvine Medical Center, Orange, California 92668
Received 11 July 1986/Accepted 3 October 1986
Although acetylsalicylic acid does not itself induce interferon, acetylsalicylic acid was found to significantly
enhance the production of both human alpha interferon and human gamma interferon when added with the
appropriate inducers to cultures of human peripheral blood mononuclear cells. The mechanisms associated
with this effect were investigated.
Prostaglandins (6, 9) and prostaglandin synthesis inhibi-
tors (4, 7, 8, 10) are known to exert a regulatory influence
oyer various components of the immune system. Interferons
(IFNs) are an important part of the immune system and thus
may be subject to the regulatory influences of prostaglan-
dins, but only the production of human gamma IFN (Hu
gamma IFN) has been shown to be affected by these
Acetylsalicylic acid (ASA) inhibits the synthesis of pros-
taglandins (13) and therefore might be expected to enhance
the yields of Hu gamma IFN. By using peripheral blood
mononuclear cells (PBMC), studies here reported have
verified that ASA improved the harvests of HU gamma IFN
but these same investigations have also shown that ASA
significantly increased the production of Hu alpha IFN.
Phytohemagglutinin P (PHA) was purchased from Difco
Laboratories, Detroit, Mich. Complexed polyinosinic-
polycytidylic acids (poly rIrC) were purchased from
Calbiochem-Behring, San Diego, Calif. Prostaglandins A1,
A2, F1, F2, and E2, as well as ASA, were purchased from
Sigma Chemical Co., St. Louis, Mo. Ibuprofen was the gift
of the Upjohn Co., Kalamazoo, Mich., and indomethacin
was obtained from Merck Sharp & Dohme, West Point, Pa.
Recombinant interleukin 2 (IL-2) was generously provided
by Cetus Instrument Systems, Emeryville, Calif. Recombi-
nant Hu alpha IFN and Hu gamma IFN were provided by S.
Pestka, Roche Institute, Nutley, N.J. Penicillin and strepto-
mycin were purchased from Pfizer Inc., New York, N.Y.
Fetal bovine serum was obtained from Irvine Scientific,
Human leukocytes were obtained as the buffy coat frac-
tion from normal human donors. Methods for the Ficoll-
Hypaque centrifugation and PHA stimulation of the cells and
for the determination of the proliferative responses have
been published previously (1, 2).
Supernatants obtained after stimulation of the PBMC were
dialyzed overnight against phosphate-buffered saline and
frozen at -80 C for subsequent lymphokine determinations.
In those experiments in which ASA or other compounds
were added to the PBMC, the reagents were freshly diluted
with phosphate-buffered saline and added to the cells simul-
taneously with the mitogen. Subsequent stimulation was
identical to that of the controls, except for the presence of
ASA or other designated reagents.
* Corresponding author.
For the induction of Hu alpha IFN, poly rIrC at a
concentration of 0.1 pg/ml was added to the PBMC (107 cells
per ml) with 250 g of DEAE-dextran per ml and was
incubated at 4 C for 30 min. We have previously found these
circumstances optimal for the induction of Hu alpha IFN. At
that time, the cells were washed three times with phosphate-
buffered saline and incubated for 24 h in RPMI 1640 medium
supplemented with 10% fetal bovine serum, 250 U of peni-
cillin per ml, and 150 g of streptomycin per ml. At the
conclusion of the incubation, the cells were removed by
centrifugation, and the supernatants were dialyzed against
phosphate-buffered saline overnight and frozen at -80 C for
assay at a later time. In those experiments in which ASA or
other reagents were added to the PBMC with the inducing
solution, appropriate controls were simultaneously prepared
which were identical to the test samples except for the
presence of ASA or other reagents.
Assays for IFN were performed in microtiter plates as
previously described (11). All IFN assays incorporated an
internal laboratory standard which had been standardized
against National Institutes of Health Hu alpha IFN standard
G-023-901-527. In this system, the titer of the reference
standard is 7,200 U/ml. All results are expressed in interna-
IL-2 was assayed by the method of Gillis et al. (5), which
relies on the determination of the uptake of [3H]thymidine by
IL-2-dependent murine (C57BL/6) tumor-specific cytotoxic
T lymphocytes (CTLL 1 and CTLL 2 cells) obtained from
James Watson, Auckland, New Zealand.
Statistical analyses were performed by comparing mean
IFN titers by the Student t test.
In the initial series of experiments, ASA, ibuprofen, and
indomethacin were shown not to influence the antiviral
activity of either recombinant Hu alpha IFN or Hu gamma
IFN. This result is consistent with the results of Tovey et al.
Table 1 demonstrates the effect of ASA on the production
of both poly rrC-induced (Hu alpha) and PHA-induced (Hu
gamma) IFNs. The yield of both species of IFN induced in
the presence of 10 jg of ASA per ml was significantly greater
(P < 0.05) than that of the controls. Yields with the higher
and lower concentrations of A$A were also increased, but
the differences were not significant compared with the con-
trols. For Hu alpha IFN, 14 experiments were performed,
and in 10 of these, yields of IFN produced in the presence of
ASA were greater than those of the controls. In the other
four experiments, the yields were equal. For Hu gamma
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Antimibrobial Agents and Chemotherapy. [Journal Article: Effect of Acetyl Salicylic Acid on Producation and Action of Leukocyte-Derived Interferons], text, January 1987; (digital.library.unt.edu/ark:/67531/metadc786200/m1/1/: accessed November 18, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Special Collections.