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Bulletin of the New York Academy of Medicine logoLink to Bulletin of the New York Academy of Medicine
. 1989 Jan;65(1):26–35.

The regulation of interferon production by aspirin, other inhibitors of the cyclooxygenase pathway and agents influencing calcium channel flux.

T C Cesario, S Yousefi, G Carandang
PMCID: PMC1807783  PMID: 2481524

Abstract

Interferon is a family of potent antiviral agents which can activate macrophages, enhance cell surface markers, or influence antibody production. Three major types of human interferon are known to exist and have been designated interferons alpha, beta, and gamma. Because of its unique antiviral properties and its ability to influence the immune response, interferon has long been considered a potential therapeutic intervention in the treatment of infections and possibly neoplastic diseases. Two potential means to utilize interferon might be considered: One method would involve the administration of exogenous interferon, but an alternative might augment natural interferon production. We have been investigating a series of pharmacological agents that might influence its production and action. Since prostaglandins influence the immune response, we have investigated the effect of these cyclic fatty acids and those agents that influence their production on soluble protein mediators of the immune response on interferon. Our studies have focused on the effects of acetylsalicylic acid on the interferon system. We have demonstrated that prostaglandins of the E series can significantly reduce the yields of human interferon gamma, but not alpha (the two species of leukocyte derived interferon). In general, yields of gamma interferon produced by peripheral blood mononuclear cells in the presence of PGE2 (0.1 to 0.01 ugm/ml) were approximately 15% of those produced in the absence of these substances. In contrast, when acetylsalicylic acid (10 ugm/ml) was added to the cultures of peripheral blood mononuclear cells yields of gamma interferon increased more than threefold. When examining the effects of acetylsalicylic acid on human alpha interferon production, we were also to enhance interferon harvests although we could not demonstrate an adverse effect of prostaglandins on the production of these bioactive proteins. Addition of acetylsalicylic acid and prostaglandins simultaneously to our cultures had a negative effect on gamma interferon production, but still was associated with enhanced yields of interferon alpha. In examining how prostaglandins might influence interferon production, we began to study other cellular requirements for lymphokine production including those processes which were calcium dependent. Preliminary studies demonstrated that production of human interferon gamma by peripheral blood mononuclear cells was calcium dependent, but production of human interferon alpha was not.(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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  1. Cesario T. C., Slater L. M. Diminished antiviral effect of human interferon in the presence of therapeutic concentrations of antineoplastic agents. Infect Immun. 1980 Mar;27(3):842–845. doi: 10.1128/iai.27.3.842-845.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cesario T. C., Slater L. M., Kaplan H. S., Gupta S., Gorse G. J. Effect of antineoplastic agents on gamma-interferon production in human peripheral blood mononuclear cells. Cancer Res. 1984 Nov;44(11):4962–4966. [PubMed] [Google Scholar]
  3. Cesario T. C., Slater L., Poo W. J., Spindler B., Walter B., Gorse G., Carandang G. The effect of hydrocortisone on the production of gamma-interferon and other lymphokines by human peripheral blood mononuclear cells. J Interferon Res. 1986 Aug;6(4):337–347. doi: 10.1089/jir.1986.6.337. [DOI] [PubMed] [Google Scholar]
  4. Dianzani F., Capobianchi M. R., Facchini J. Role of calcium in gamma interferon induction: inhibition by calcium entry blockers. J Virol. 1984 Jun;50(3):964–965. doi: 10.1128/jvi.50.3.964-965.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dianzani F., Monahan T. M., Georgiades J., Alperin J. B. Human immune interferon: induction in lymphoid cells by a calcium ionophore. Infect Immun. 1980 Aug;29(2):561–563. doi: 10.1128/iai.29.2.561-563.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ikossi M. G., Ambrus J. L., Chadha K. C. Regulation of in vitro human leukocyte interferon production: effect of prostaglandin synthetase and phosphodiesterase inhibition. Res Commun Chem Pathol Pharmacol. 1986 Dec;54(3):379–393. [PubMed] [Google Scholar]
  7. Murray H. W. Interferon-gamma, the activated macrophage, and host defense against microbial challenge. Ann Intern Med. 1988 Apr;108(4):595–608. doi: 10.7326/0003-4819-108-4-595. [DOI] [PubMed] [Google Scholar]
  8. Rasmussen H. The calcium messenger system (2). N Engl J Med. 1986 May 1;314(18):1164–1170. doi: 10.1056/NEJM198605013141807. [DOI] [PubMed] [Google Scholar]
  9. Reem G. H., Yeh N. H. Interleukin 2 regulates expression of its receptor and synthesis of gamma interferon by human T lymphocytes. Science. 1984 Jul 27;225(4660):429–430. doi: 10.1126/science.6429853. [DOI] [PubMed] [Google Scholar]
  10. Schramm M., Thomas G., Towart R., Franckowiak G. Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels. Nature. 1983 Jun 9;303(5917):535–537. doi: 10.1038/303535a0. [DOI] [PubMed] [Google Scholar]
  11. Storch E., Kirchner H., Hüller K., Martinotti M. G., Gemsa D. Enhancement by carprofen or indomethacin of interferon induction by 10-carboxymethyl-9-acridanone in murine cell cultures. J Gen Virol. 1986 Jun;67(Pt 6):1211–1214. doi: 10.1099/0022-1317-67-6-1211. [DOI] [PubMed] [Google Scholar]
  12. Vervliet G., Deckmyn H., Carton H., Billiau A. Influence of prostaglandin E2 and indomethacin on interferon-gamma production by cultured peripheral blood leukocytes of multiple sclerosis patients and healthy donors. J Clin Immunol. 1985 Mar;5(2):102–108. doi: 10.1007/BF00915007. [DOI] [PubMed] [Google Scholar]
  13. Wakasugi N., Virelizier J. L., Arenzana-Seisdedos F., Rothhut B., Huerta J. M., Russo-Marie F., Fiers W. Defective IFN-gamma production in the human neonate. II. Role of increased sensitivity to the suppressive effects of prostaglandin E. J Immunol. 1985 Jan;134(1):172–176. [PubMed] [Google Scholar]
  14. Yousefi S., Chiu J., Carandang G., Archibeque E. G., Vaziri N., Cesario T. C. Effect of acetyl salicylic acid on production and action of leukocyte-derived interferons. Antimicrob Agents Chemother. 1987 Jan;31(1):114–116. doi: 10.1128/aac.31.1.114. [DOI] [PMC free article] [PubMed] [Google Scholar]

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