Abstract
The effects of human immunoglobulin preparations for intravenous use (IVIg) on in vitro-induced monokine production were studied. Individual peripheral blood monocytes, obtained from healthy blood donors, which produced interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) after in vitro stimulation, were identified by cytokine-specific monoclonal antibodies (mAb) and indirect immunofluorescence technique. Lipopylosaccharide (LPS) or Borrelia burgdorferi spirochetes (Bb) were used to induce TNF-alpha and IL-6 production in cultures. Peak synthesis occurred 2.5 hr after initiation of the cultures in the majority of the monocytes, but not at all in lymphocytes. The monocytes were identified by two-colour staining using a monocyte-specific mAb. IL-6 was produced by 64 +/- 8% or 71 +/- 9% (means +/- SD) of the non-IVIg-exposed monocytes after LPS or Bb stimulation, respectively (n = 12). A dose-dependent and significant reduction of the number of IL-6-producing cells was noted in the IVIg-supplemented cultures (P less than 0.003). In these cultures 24 +/- 12% or 29 +/- 12% of the monocytes made IL-6 in response to LPS or Bb. Kinetic studies indicated a sustained significant inhibition of IL-6 production during 24 hr of culture (P less than 0.001). In contrast, TNF-alpha synthesis was not inhibited by IVIg. LPS or Bb stimulation resulted in 47 +/- 18% or 69 +/- 7% TNF-alpha producing cells versus 48 +/- 9% or 59 +/- 8% in IVIg-supplemented cultures. These results indicate down-regulation of IL-6, but not TNF-alpha production, by IVIg. A direct antigen neutralization is an unlikely explanation for the divergent effects observed on monokine production after IVIg addition.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ammann A. J., Ashman R. F., Buckley R. H., Hardie W. R., Krantmann H. J., Nelson J., Ochs H., Stiehm E. R., Tiller T., Wara D. W. Use of intravenous gamma-globulin in antibody immunodeficiency: results of a multicenter controlled trial. Clin Immunol Immunopathol. 1982 Jan;22(1):60–67. doi: 10.1016/0090-1229(82)90022-8. [DOI] [PubMed] [Google Scholar]
- Andersson U., Matsuda T. Human interleukin 6 and tumor necrosis factor alpha production studied at a single-cell level. Eur J Immunol. 1989 Jun;19(6):1157–1160. doi: 10.1002/eji.1830190629. [DOI] [PubMed] [Google Scholar]
- Beck G., Habicht G. S., Benach J. L., Coleman J. L. Chemical and biologic characterization of a lipopolysaccharide extracted from the Lyme disease spirochete (Borrelia burgdorferi). J Infect Dis. 1985 Jul;152(1):108–117. doi: 10.1093/infdis/152.1.108. [DOI] [PubMed] [Google Scholar]
- Berkman S. A., Lee M. L., Gale R. P. Clinical uses of intravenous immunoglobulins. Ann Intern Med. 1990 Feb 15;112(4):278–292. doi: 10.7326/0003-4819-112-4-278. [DOI] [PubMed] [Google Scholar]
- Bussel J., Pahwa S., Porges A., Cunningham-Rundles S., Koziner B., Morell A., Barandun S. Correlation of in vitro antibody synthesis with the outcome of intravenous gamma-globulin treatment of chronic idiopathic thrombocytopenic purpura. J Clin Immunol. 1986 Jan;6(1):50–56. doi: 10.1007/BF00915364. [DOI] [PubMed] [Google Scholar]
- Furusho K., Kamiya T., Nakano H., Kiyosawa N., Shinomiya K., Hayashidera T., Tamura T., Hirose O., Manabe Y., Yokoyama T. High-dose intravenous gammaglobulin for Kawasaki disease. Lancet. 1984 Nov 10;2(8411):1055–1058. doi: 10.1016/s0140-6736(84)91504-6. [DOI] [PubMed] [Google Scholar]
- Henter J. I., Söder O., Andersson U. Identification of individual tumor necrosis factor/cachectin-producing cells after lipopolysaccharide induction. Eur J Immunol. 1988 Jul;18(7):983–988. doi: 10.1002/eji.1830180703. [DOI] [PubMed] [Google Scholar]
- Leung D. Y., Cotran R. S., Kurt-Jones E., Burns J. C., Newburger J. W., Pober J. S. Endothelial cell activation and high interleukin-1 secretion in the pathogenesis of acute Kawasaki disease. Lancet. 1989 Dec 2;2(8675):1298–1302. doi: 10.1016/s0140-6736(89)91910-7. [DOI] [PubMed] [Google Scholar]
- Lonnemann G., Endres S., Van der Meer J. W., Cannon J. G., Koch K. M., Dinarello C. A. Differences in the synthesis and kinetics of release of interleukin 1 alpha, interleukin 1 beta and tumor necrosis factor from human mononuclear cells. Eur J Immunol. 1989 Sep;19(9):1531–1536. doi: 10.1002/eji.1830190903. [DOI] [PubMed] [Google Scholar]
- Montanaro A., Pirofsky B. Prolonged interval high-dose intravenous immunoglobulin in patients with primary immunodeficiency states. Am J Med. 1984 Mar 30;76(3A):67–72. doi: 10.1016/0002-9343(84)90322-x. [DOI] [PubMed] [Google Scholar]

