Skip to main content
Log in

Effects of immunoglobulin and gamma-interferon on the production of tumour necrosis factor-α and interleukin-1β by peripheral blood monocytes in the acute phase of Kawasaki disease

  • Immunology/Allergology
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Abstract

In order to study the in vitro effects of intact immunoglobulin (Ig) and gamma-interferon (INF-γ) in patients with Kawasaki disease, the production of tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was measured in peripheral blood monocytes (PBM) both before and after intravenous immunoglobulin (IVIG) therapy. Spontaneous production of TNF-α and IL-1β both before and after IVIG therapy was significantly higher than in healthy controls. Intact Ig enhanced in vitro the production of TNF-α and IL-1β both before and after IVIG therapy approximately 3–4 times as compared to the spontaneous production. INF-γ did not affect the production of the two cytokines. Ig enhanced IL-1β mRNA expression in PBM of KD by 3–8 times more than that of spontaneous production.

Conclusion

These results suggest that: (1) the mechanism of action of IVIG therapy in KD is not to cut down the production of inflammatory cytokines such as TNF-α and IL-1β andf that (2) the changes of these cytokine levels may be related to the clinical effectiveness of high dose IVIG.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

Ig :

immunoglobulin

IL-1β:

interleukin-1β

INF :

γ/gamma-interferon

IVIG :

intravenous imm unoglobulin

KD :

Kawasaki disease

PBM :

peripheral blood monocytes

TNF-α:

tumour necrosis factor-α

References

  1. Anderson JP, Anderson UG (1990) Human intravenous immunoglobulin modulates monokine production in vitro. Immunology 71:372–376

    PubMed  Google Scholar 

  2. Andersson UG, Bjork L, Skansen-Saphir U, Andersson JP (1993) Down-regulation of cytokine production and interleukin-2 receptor expression by pooled IgG. Immunology 79:211–216

    PubMed  Google Scholar 

  3. Berkman SA, Lee ML, Gale RP (1990) Clinical use of intravenous immunoglobulins. Ann Intern Med 112:278–292

    PubMed  Google Scholar 

  4. Debets JMH, Van Der Linden CJ, Dieteren IEM, Leeuwenberg JFM, Buurman WA (1988) Fc-receptor crosslinking induces rapid secretion of tumor necrosis factor (cachectin) by human peripheral blood monocytes. J Immunol 141:1197–1201

    PubMed  Google Scholar 

  5. Dwyer JM (1992) Manipulating the immune system with immune globulin. N Engl J Med 326:107–116

    PubMed  Google Scholar 

  6. Furukawa S, Matsubara T, Jujoh K, Yone K, Sugawara T, Sasai K, et al (1988) Peripheral blood monocyte/ macrophages and serum tumor necrosis factor in Kawasaki disease. Clin Immunol Immunopathol 48:247–251

    PubMed  Google Scholar 

  7. Furusho K, Kamiya T, Nakano H, Kiosawa N, Shinomyia K, Hayashida T, et al (1984) High dose intravenous gammaglobulin for Kawasaki disease. Lancet II:1055–1058

    Google Scholar 

  8. Gifford GE, Lohmann-Matthes ML (1987) Gamma interferon priming of mouse and human macrophages for induction of tumor necrosis factor production by bacterial lipopolysaccharide. J Natl Cancer Inst 78:121–124

    PubMed  Google Scholar 

  9. Harada K, Yamaguchi H, Hase N, Sato T, Asai T, Tatara K, et al (1988) Intravenous gammaglobulin treatment in Kawasaki disease. Presented at the Third International Kawasaki Disease Symposium, Tokyo, Japan, Proceedings, pp 314–317

  10. Iizuka T, Minatogawa Y, Suzuki H, Mutsumi Ito, Shigeru Nakamine, Yoshihumi Hatanaka, et al (1993) Urinary neopterin as a predictive marker of coronary artery abnormalities in Kawasaki syndrome. Clin Chem 39:600–604

    PubMed  Google Scholar 

  11. Kawasaki T (1967) Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children: clinical observation of 50 cases. Jpn J Allergol 16:178–222

    Google Scholar 

  12. Kawasaki T, Kosaki F, Okawa S, Shigematsu I, Yanagawa H (1974) A new infantile acute febrile mucokutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics 54:271–276

    PubMed  Google Scholar 

  13. Lang BA, Silverman ED, Laxer RM, Lau AS (1989) Spontaneous tumor necrosis factor production in Kawasaki disease. J Pediatr 115:939–943

    PubMed  Google Scholar 

  14. Leung DYM, Cotran RS, Kurt-Jomes E, Burns JC, Newburger JW, Pober JS (1989) Endothelial cell activation and high interleukin-1 secretion in the pathogenesis of acute Kawsaki disease. Lancet II:1298–1302

    Google Scholar 

  15. Lin C-Y, Lin C-C, Hwang B, Chiang BN (1991) The changes of interleukin-2, tumor necrotic factor and gamman-interferon production among patients with Kawasaki disease. Eur J Pediatr 150:179–182

    PubMed  Google Scholar 

  16. Ling Z-D, Yeoh E, Webb BT, Farrell K, Doucette J, Matheson DS (1993) Intravenous Immunoglobulin induces Interferon- and interleukin-6 in vivo. J Clin Immunol 13:302–309

    PubMed  Google Scholar 

  17. Maury CPJ, Salo E, Pelkonen P (1989) Elevated circulating tumor necrosis factor-α in patients with Kawasaki disease. J Lab Clin Med 113:651–654

    PubMed  Google Scholar 

  18. Newburger JW, Takahashi M, Burns JC, Beiser AS, Chung KJ, et al (1986) The treatment of Kawasaki syndrome with intravenous gammaglobulin. N Engl J M 315:341–347

    PubMed  Google Scholar 

  19. Newburger JW, Takahashi M, Beiser AS, Burns JC, Bastian J, Chung KJ, et al (1991) A single intravenous infusions in the treatment of acute Kawasaki syndrome. N Engl J Med 324:1633–1639

    PubMed  Google Scholar 

  20. Okuni M, Harada K, Yamaguchi H, Yanagawa H, Sonobe T, Kawasaki T (1987) Intravenous Gammaglobulin therapy in Kawasaki disease: trial of low-dose gamma globulin. In: Shulman ST (ed) Kawasaki disease. Alan R Liss. New York, pp 433–439

    Google Scholar 

  21. Pål Aukrust, Stig S. Frøland, Nina-Beate Liabakk, Fredrik Müller, Ingvild Nordøy, Charlotte Haug, Terje Espevik (1994) Release of cytokines, soluble cytokine receptors, and interleukine-1 receptor antagonist after intravenous immunoglobulin administration in vivo. Blood 84:2136–2143

    PubMed  Google Scholar 

  22. Research Committee on Kawasaki Disease (1984) Report of Subcommittee on standardization of diagnostic criteria and reporting of coronary artery lesion in Kawasaki disease. Tokyo, Japan, Ministry of Health and Welfare, pp 55–66

    Google Scholar 

  23. Rosen FS (1993) Putative mechanisms of the effect of intravenous γ-globulin. Clin Immunol Immunopathol 67 [Suppl]:S41-S43

    PubMed  Google Scholar 

  24. Rowley AH, Shulman ST (1991) Current therapy for acute Kawasaki syndrome. J Pediatr 118:987–991

    PubMed  Google Scholar 

  25. Shigenobu Tone, Yuko Katoh, Hirokazu Fujimoto, Shin Togashi, Masako Yanazawa, Yoshihiro Kato, et al (1990) Exression of inhibin a-subunit gene during mouse gametogenesis. Differentiation 44:62–68

    PubMed  Google Scholar 

  26. Shimozato T, Iwata M, Tamura N (1990) Suppression of tumor necrosis factor alpha production by a human immunoglobulin preparation for intravnous use. Infect Immun 58:1384–1390

    PubMed  Google Scholar 

  27. Shulman ST (1989) IVGG therapy in Kawsaki disease: mechanism of action. Clin Immunol Immunopathol 53:141–146

    Google Scholar 

  28. Suzuki H, Iizuka T, Uemura S, Koike M, Maeda J (1988) The pathophysiological significance of serum tumor necrosis factor in Kawasaki disease. Presented at the Third International Kawasaki Disease Symposium, Tokyo, Japan, Proceedings, pp 117–119

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Suzuki, H., Uemura, S., Tone, S. et al. Effects of immunoglobulin and gamma-interferon on the production of tumour necrosis factor-α and interleukin-1β by peripheral blood monocytes in the acute phase of Kawasaki disease. Eur J Pediatr 155, 291–296 (1996). https://doi.org/10.1007/BF02002715

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02002715

Key words

Navigation