Skip to main content
SpringerLink
Log in

Nonsteroidal Anti-inflammatory Drugs: Effects on Lymphocyte Function

  • Chapter
The Pharmacology of Lymphocytes

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 85))

Abstract

The pioneering work of Morley (for review see Morley 1978) has indicated that prostaglandins (PG) are regulators of immune functions in vivo (see Chap. 16); nonsteroidal anti-inflammatory drugs (NSAID), on the other hand, are known to interfere with PG synthesis (Vane 1971). Consequently, experimental and clinical effects of NSAID on immune functions in vivo and in vitro have been postulated for more than a decade (for reviews see Bray 1980; Goodwin and Webb 1980; Goodwin and Ceuppens 1983). Nevertheless, a clear-cut definition of the impact of NSAID at clinical dosage on immune functions is still lacking, and the contribution of these putative effects to therapeutic results remains elusive. Moreover, the experimental basis of assumptions about possible clinical effects remains meagre. The situation is very well described by Goddwin and Ceuppens (1983). They state in their review on Regulation of the Immune Response by Prostaglandins (p. 304):

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Anderson CB, Jaffee BM, Graff RJ (1977) Prolongation of murine skin allografts by prostaglandin El. Transplantation 23: 444–449

    Article  PubMed  CAS  Google Scholar 

  • Bacon PA (1984) Nonsteroidal anti-inflammatory drugs and immunologic function. Overview of the European experience. Am J Med 77: 26–31

    PubMed  CAS  Google Scholar 

  • Binderup L (1983) Lymphocyte-macrophage co-operation during induction of T-sup-pressor cell activity in rats with adjuvant arthritis. Ann Rheum Dis 42: 687–692

    Article  PubMed  CAS  Google Scholar 

  • Bray MA (1980) Prostaglandins: fine tuning the immune system? Immunol Today 9: 65–69

    Article  Google Scholar 

  • Brune K (1985) Tissue accumulation of non-steroidal anti-inflammatory drugs. In: Nilsen OG (ed) Tiaprofenic acid. Pharmacology and pharmacokinetics communications. Excerpta Medica, Amsterdam, pp 31–37

    Google Scholar 

  • Brune K, Lanz R (1984) Nonopioid analgesics. In: Kuhar M, Pasternak G (eds) Analgesics: neurochemical, behavioral and clinical perspectives. Raven, New York, pp 149–173

    Google Scholar 

  • Brune K, Lanz R (1985) Pharmacokinetics of non-steroidal anti-inflammatory drugs. In: Bonta IL, Bray MA, Parnham MJ (eds) Handbook of inflammation, vol 5. Elsevier, Amsterdam, pp 413–449

    Google Scholar 

  • Brune K, Whitehouse MW (1978) Cytostats with effects in chronic inflammation. In: Vane JR, Ferreira SH (eds) Handbook of experimental pharmacology, vol 50/II. Springer, Berlin Heidelberg New York, pp 531–578

    Google Scholar 

  • Brune K, Glatt M, Graf P (1976) Mechanisms of action of anti-inflammatory drugs. Gen Pharmacol 7: 27–33

    Article  PubMed  CAS  Google Scholar 

  • Brune K, Rainsford KD, Wagner K, Peskar A (1981) Inhibition by anti-inflammatory drugs of prostaglandin production in cultures macrophages. Naunyn-Schmiedebergs Arch Pharmacol 315: 269–276

    Article  PubMed  CAS  Google Scholar 

  • Ceuppens J, Goodwin JS (1982) Endogenous prostaglandin E enhances polyclonal immunoglobulin production by tonically inhibiting T suppressor cell activity. Cell Immunol 70: 41–54

    CAS  Google Scholar 

  • Ceuppens JL, Rodriguez MA, Goodwin JS (1982) Non-steroidal anti-inflammatory agents inhibit the synthesis of IgM rheumatoid factor in vitro.

    Google Scholar 

  • Ciosek CP, Ortel RW, Thanassi NM, Newcombe DS (1974 a) Indomethacin potentiates PGE1 stimulated cyclic AMP accumulation in human synoviocytes. Nature 251: 148–150

    Google Scholar 

  • Ciosek CP, Ortel RW, Thanassi NM, Newcombe DS (1974 b) Inhibition of phosphodiesterase by non steroidal anti-inflammatory drugs. Nature 251: 148–150

    Google Scholar 

  • Cook R (1978) Regulation of the in vitro anamnestic antibody response by cyclic AMP. II. Prostaglandins of the E series. Cell Immunol 40: 128–133

    Article  CAS  Google Scholar 

  • Droller MJ, Gomolka D (1983) Enhancement of natural cytotoxicity in lymphocytes from animals with carcinogen-induced bladder cancer. J Urol 129: 625–629

    PubMed  CAS  Google Scholar 

  • Emery P, Panayi GS, Nouri ME (1984) Interleukin-2 reverses deficient cell-mediated immune responses in rheumatoid arthritis. Clin Exp Immunol 57: 123–129

    PubMed  CAS  Google Scholar 

  • Etienne J, Polonovski J (1984) Phospholipase A2 activity in rat and human lymphocytes. Biochem Biophys Res Corn 125: 719–727

    Article  CAS  Google Scholar 

  • Ezdinli EZ, Kucuk O et al. (1986) Hypogammaglobulinemia and hemophagocytic syndrome associated with lymphoproliferative disorders. Cancer 57: 1024–1037

    Article  PubMed  CAS  Google Scholar 

  • Ferreira SH, Vane JR (1978) Mode of action of anti-inflammatory agents which are prostaglandin synthetase inhibitors. In: Vane JR, Ferreira SH (eds) Handbook of experimental pharmacology, vol 50/II. Springer, Berlin Heidelberg New York, pp 348–398

    Google Scholar 

  • Floersheim GL (1965) Pharmakologische Beeinflußbarkeit cellulärer Immunität. Z Naturwiss Med Grundlagenforsch 2: 307–365

    PubMed  CAS  Google Scholar 

  • Flower RJ (1974) Drugs which inhibit prostaglandin biosynthesis. Pharmacol Rev 26: 3367

    Google Scholar 

  • Forre O, Thoen J, Helgetveit K, Haile Y (1984) Nonsteroidal anti-inflammatory drugs in rheumatoid arthritis. Inflammation [Suppl] 9: 109–113

    Google Scholar 

  • Garin EH, Barran TM (1982) Effects of indomethacin on lymphocyte response to mitogens in puromycin aminonucleoside nephrosis in the rat. Clin Exp Immunol 49: 639–644

    PubMed  CAS  Google Scholar 

  • Garin EH, Sausville PJ, Richard GA (1983) Serum inhibitor of phytohemagglutinin-in-duced lymphocyte proliferation in Bartter syndrome. J Pediatr 102: 569–572

    Article  PubMed  CAS  Google Scholar 

  • Goodacre RL, Bienenstock J (1982) Reduced suppressor cell activity in intestinal lympho-cytes from patients with Crohn’s disease. Gastroenterology 82: 653–658

    PubMed  CAS  Google Scholar 

  • Goodwin JS, Ceuppens J (1983) Regulation of the immune response by prostaglandins. J Clin Immunol 3: 295–315

    Article  PubMed  CAS  Google Scholar 

  • Goodwin JS, Webb DR (1980) Regulation of the immune response by prostaglandins. Clin Immunol Immunopathol 15: 106–122

    Article  PubMed  CAS  Google Scholar 

  • Goodwin JS, Bankhurst AD, Murphy S, Selinger DS, Messner RP, Williams RC jr (1978) Partial reversal of the cellular immune defect in common variable immunodeficiency with indomethacin. J Clin Lab Immunol 1: 197–204

    PubMed  CAS  Google Scholar 

  • Goodwin JS, Messner RP, Peake GT ( 1978 a) Prostaglandin suppression of mitogen-stimulated lymphocytes in vitro. Changes with mitogen dose and preincubation. J Clin Invest 62: 753–760

    Google Scholar 

  • Goodwin JS, Selinger DS, Messner RP, Reed WP (1978 b) Effect of indomethacin in vivo on humoral and cellular immunity in humans. Infect Immun 19: 430–433

    Google Scholar 

  • Goodwin JS, Ceuppens JL, Rodriguez MA (1984) Effect of non-steroidal anti-inflammatory agents on immunologic function in patients with rheumatoid arthritis. Inflammation [Suppl] 8: 49–55

    Google Scholar 

  • Gordon D, Bray MA, Morley J (1976) Control of lymphokine secretion by prostaglandins. Nature 262: 401–402

    Article  PubMed  CAS  Google Scholar 

  • Greene BM, Fanning MM, Ellner JJ (1983) Non-specific suppression of antigen-induced lymphocyte blastogenesis in Onchocerca volvulus infection in man. Clin Exp Immunol 52: 259–265

    PubMed  CAS  Google Scholar 

  • Grohmann P, Porzsolt F, Quirt I, Miller R, Phillips R (1981) Stimulation of human NK cell activity by cultured cells. Clin Exp Immunol 44: 611–614

    PubMed  CAS  Google Scholar 

  • Hallgren HM, Yunis EJ (1977) Suppressor lymphocytes in young and aged humans. J Immunol 118: 1004–1009

    Google Scholar 

  • Hasler F, Bluestein HG, Zvaifler NJ, Epstein LB (1983) Analysis of the defects responsible for the impaired regulation of EBV-induced B cell proliferation by rheumatoid arthritis lymphocytes. II. Role of monocytes and the increased sensitivity of rheumatoid arthritis lymphocytes to prostaglandin El. J Immunol 131: 768–772

    Google Scholar 

  • Helleberg L (1981) Clinical pharmacokinetics of indomethacin. Clin Pharmacol 6: 245–258

    Article  CAS  Google Scholar 

  • Hofer D, Duibitsky AM, Reilly P, Santoro MG, Jaffee BM (1980) The interactions between indomethacin and cytotoxic drugs in mice bearing B-16 melanomas. Prostaglandins 20: 1033–1039

    Article  PubMed  CAS  Google Scholar 

  • Humes JL, Winter CA, Sadowski SJ, Kuehl FA (1981) Multiple sites on prostaglandin cyclooxygenase are determinants in the action of nonsteroidal antiinflammatory agents. Proc Natl Acad Sci USA 78: 2053–2056

    Article  PubMed  CAS  Google Scholar 

  • Johnsen S, Olding LB, Westberg NG, Wilhelmsson L (1982) Strong suppression by mononuclear leukocytes from human newborns on maternal leukocytes: mediation by prostaglandins. Clin Immunol Immunopathol 23: 606–615

    Article  PubMed  CAS  Google Scholar 

  • Kantor HS, Hampton M (1978) Indomethacin in submicromolar concentrations inhibits cyclic AMP-dependent protein kinase. Nature 276: 841–842

    Article  PubMed  CAS  Google Scholar 

  • Karim SMM, Rao B (1976) Prostaglandins and tumors. In: Karim SMM (ed) Prostaglandins: physiological, pharmacological and pathological aspects. MTP Press, Lancaster, pp 303–325

    Google Scholar 

  • Kunkel SB, Chensue SW (1985) Arachidonic acid metabolites regulate interleukin-1 production. Biochem Biophys Res Commun 128: 892–897

    Article  PubMed  CAS  Google Scholar 

  • Kurland JI, Kincade PW, Moore MAS (1977) Regulation of B-lymphocyte clonal proliferation by stimulatory and inhibitory macrophage-derived factors. J Exp Med 146: 1420–1435

    Article  PubMed  CAS  Google Scholar 

  • Lammie PJ, Katz SP (1983) Immunoregulation in experimental filariasis. I. In vitro suppression of mitogen-induced blastogenesis by adherent cells from jirds chronically infected with brugia pahangi. J Immunol 130: 1381–1385

    Google Scholar 

  • Leclerc C, Morin A, Deriaud E, Chedid L (1984) Inhibition of human IL 2 production by MDP and derivates. J Immunol 133: 1996–2000

    PubMed  CAS  Google Scholar 

  • Lewis GP, Barrett ML (1986) Immunosuppressive actions of prostaglandins and the possible increase in chronic inflammation after cyclooxygenase inhibitors. Agents Actions 19: 59–65

    Article  PubMed  CAS  Google Scholar 

  • Lipsmeyer E (1982) Effect of cimetidine and indomethacin on delayed hypersensitivity. Transplantation 33: 107–113

    Article  PubMed  CAS  Google Scholar 

  • Lynch NR, Salomon J (1979) Tumor growth inhibition and potentiation of immunotherapy by indomethacin in mice. J Natl Cancer Inst 62: 117–121

    PubMed  CAS  Google Scholar 

  • Lynch NR, Casatles M, Astonin M, Salomon JC (1978) Mechanism of inhibition of tumor growth by aspirin and indomethacin. Br J Cancer 38: 503–509

    Article  PubMed  CAS  Google Scholar 

  • Maca RD, Panje WR (1982) Indomethacin sensitive suppressor cell activity in head and neck cancer patients pre-and postirradiation therapy. Cancer 50: 483–489

    Article  PubMed  CAS  Google Scholar 

  • Mahowald ML, Dalmasso AP, Messner RP (1983) Endogenous inhibition of autologous lymphocyte antibody-dependent cellular cytotoxicity. Clin Immunol Immunopathol 29: 211–222

    Article  PubMed  CAS  Google Scholar 

  • Morley J (1978) Lymphokines. In: Vane JR, Ferreira SH (eds) Handbook of experimental pharmacology, vol 50/I. Springer, Berlin Heidelberg New York, pp 314–342

    Google Scholar 

  • Muscoplat CC, Rakich PM, Thoen CO, Johnson DW (1978) Enhancement of lymphocyte blastogenic and delayed hypersensitivity skin responses by indomethacin. Infect Immun 20: 627–632

    PubMed  CAS  Google Scholar 

  • Palmer DG, Barbezat GO, Gibbins BL, Grennan DM, Lum J, Myers DB, Wilson K (1981) A single-blind crossover trial of the anti-inflammatory drug sodium meclofenamate and placebo, including an evaluation of hand grip and of lymphocyte responsiveness. Curr Med Res Opin 7: 359–367

    PubMed  CAS  Google Scholar 

  • Palmer DG, Ferry DG, Gibbins DL, Hall SM, Grennan DM, Lum J, Myers DB (1982) Ibuprofen and diflunisal in rheumatoid arthritis: a double blind comparative trial. NZ Med J 2: 45–48

    Google Scholar 

  • Panayi GS, Staite ND, Unger A (1981) Indomethacin inhibits in vitro immunoglobulin production by human B lymphocytes. Agents Actions 11: 608–610

    Article  PubMed  CAS  Google Scholar 

  • Panje WR (1981) Regression of head and neck carcinoma with a prostaglandin synthesis inhibitor. Arch Otolaryngol 107: 658–663

    Article  PubMed  CAS  Google Scholar 

  • Rappaport RS, Dodge GR (1982) Prostaglandins E inhibits the production of human interleukin 2 J Exp Med 155: 943–948

    CAS  Google Scholar 

  • Reddy MM, Manvar D, Ahuja KK, Moriarty ML, Grieco MH (1985) Augmentation of mitogen-induced proliferative reponses by in vitro indomethacin in patients with acquired immune deficiency syndrome and AIDS-related complex. Int J Immunopharmacol 7: 917–921

    Article  PubMed  CAS  Google Scholar 

  • Rojo JM, Barasoain I, Portoles A (1981) Further studies on the immunosuppressive effects of indomethacin. Int J Clin Pharmacol Ther Toxicol 19: 220–222

    PubMed  CAS  Google Scholar 

  • Salmon M, Bacon PA, Johnson GD, Walton KW (1984) The use of cytocentrifuge preparations for the demonstration of T cell surface antigens. J Immunol Methods 66: 327–330

    Article  PubMed  CAS  Google Scholar 

  • Smiley J, Sachs C, Ziff M (1968) In vitro synthesis of immunoglobulin by rheumatoid synovial membrane. J Clin Invest 47: 624–632

    Article  PubMed  CAS  Google Scholar 

  • Staite ND, Panayi GS (1982) Regulation of human immunoglobulin production in vitro by prostaglandin E2. Clin Exp Immunol 49: 115–122

    PubMed  CAS  Google Scholar 

  • Tilden AB, Balch CM (1982) Immune modulatory effects of indomethacin in melanoma patients are not related to prostaglandin E2-mediated suppression. Surgery 92: 528–532

    PubMed  CAS  Google Scholar 

  • Tosato G, Steinberg AD, Blaese RM (1981) Defective EB virus-specific suppressor cell function in rheumatoid arthritis. N Engl J Med 305: 1238–1244

    Article  PubMed  CAS  Google Scholar 

  • Tracey DE, Adkinson NF (1980) Prostaglandin synthesis inhibitors potentiate the BCG-induced augmentation of natural killer cell activity. J Immunol 125: 136–141

    PubMed  CAS  Google Scholar 

  • Vane JR (1971) Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature New Biol 231: 232–235

    PubMed  CAS  Google Scholar 

  • Webb DR, Osheroff PK (1976) Antigen stimulation of prostaglandin synthesis and control of immune responses. Proc Natl Acad Sci USA 73: 1300–1309

    Article  PubMed  CAS  Google Scholar 

  • Wiedner KJ, Webb DR (1981) The effect of prostaglandin metabolism on immunoglobulin and antibody production in naive and educated whole spleen cells. Prostaglandins Leukotrienes Med 7: 79–90

    Google Scholar 

  • Zimecki M, Webb DR (1976) The regulation of the immune response to T-independent antigens by prostaglandins and B cells. J Immunol 117: 2158–2164

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. K. Brune
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Research Department, CIBA-GEIGY AG, CH-4002, Basel, Switzerland

    Michael A. Bray Ph. D.

  2. Pharmaceutical Division, Preclinical Research, SANDOZ Ltd., CH-4002, Basel, Switzerland

    John Morley Ph. D., FRC Path.

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Brune, K. (1988). Nonsteroidal Anti-inflammatory Drugs: Effects on Lymphocyte Function. In: Bray, M.A., Morley, J. (eds) The Pharmacology of Lymphocytes. Handbook of Experimental Pharmacology, vol 85. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73217-1_27

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-73217-1_27

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-73219-5

  • Online ISBN: 978-3-642-73217-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation