Abstract
Monoclonal antibodies (MAbs) against two non-cross-reacting antigens of human IL-1 beta (Vhp20 and BRhC3) and human TNF alpha (B154.2 and B154.7) were applied to identify cytokine-containing cells in tissue sections and in cell suspensions. IL-1 beta- or TNF alpha-positive cells were not present in immunostained cytocentrifuge smears prepared from freshly isolated peripheral blood leukocytes, spleen, and lymph node cells. After 18 hours of culture with bacterial endotoxin (LPS), 80% to 90% of blood monocytes, 30% of spleen macrophages, and 2% to 28% of lymph node macrophages were strongly positive for IL-1 beta with either of the MAbs. Furthermore, 25% to 35% of blood monocytes and 6% to 60% of lymph node macrophages were stained for TNF alpha. Cells positive for IL-1 beta or TNF alpha were extremely rare in sections of normal thymus, spleen, and lymph nodes. Immunoreactivity for IL-1 beta or TNF alpha was frequently observed in sections of granulomatous lymphadenitis (N = 11). IL-1 beta or TNF alpha staining was confined to the epithelioid macrophages forming the granuloma, and the intensity of TNF alpha reactivity was generally stronger. The high frequency of cytokine-containing cells in this pathologic condition was confirmed in a cell suspension study showing that 20% of epithelioid macrophages were weakly positive for IL-1 beta and 80% were strongly positive for TNF alpha. The presence of cytokine-containing cells was investigated in cryostat sections of several nonlymphoid organs with normal histologic appearance. IL-1 beta reactivity was not observed in any of the tissues. TNF alpha reactivity was frequently demonstrated in isolated macrophages embedded in the interstitial connective tissue.
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.
- Bayne E. K., Rupp E. A., Limjuco G., Chin J., Schmidt J. A. Immunocytochemical detection of interleukin 1 within stimulated human monocytes. J Exp Med. 1986 May 1;163(5):1267–1280. doi: 10.1084/jem.163.5.1267. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bernaudin J. F., Yamauchi K., Wewers M. D., Tocci M. J., Ferrans V. J., Crystal R. G. Demonstration by in situ hybridization of dissimilar IL-1 beta gene expression in human alveolar macrophages and blood monocytes in response to lipopolysaccharide. J Immunol. 1988 Jun 1;140(11):3822–3829. [PubMed] [Google Scholar]
- Beutler B., Cerami A. The common mediator of shock, cachexia, and tumor necrosis. Adv Immunol. 1988;42:213–231. doi: 10.1016/s0065-2776(08)60846-9. [DOI] [PubMed] [Google Scholar]
- Bohnsack J. F., Kleinman H. K., Takahashi T., O'Shea J. J., Brown E. J. Connective tissue proteins and phagocytic cell function. Laminin enhances complement and Fc-mediated phagocytosis by cultured human macrophages. J Exp Med. 1985 May 1;161(5):912–923. doi: 10.1084/jem.161.5.912. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burchett S. K., Weaver W. M., Westall J. A., Larsen A., Kronheim S., Wilson C. B. Regulation of tumor necrosis factor/cachectin and IL-1 secretion in human mononuclear phagocytes. J Immunol. 1988 May 15;140(10):3473–3481. [PubMed] [Google Scholar]
- Chilosi M., Menestrina F., Capelli P., Montagna L., Lestani M., Pizzolo G., Cipriani A., Agostini C., Trentin L., Zambello R. Immunohistochemical analysis of sarcoid granulomas. Evaluation of Ki67+ and interleukin-1+ cells. Am J Pathol. 1988 May;131(2):191–198. [PMC free article] [PubMed] [Google Scholar]
- Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
- Cuturi M. C., Murphy M., Costa-Giomi M. P., Weinmann R., Perussia B., Trinchieri G. Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes. J Exp Med. 1987 Jun 1;165(6):1581–1594. doi: 10.1084/jem.165.6.1581. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dinarello C. A. Interleukin-1. Rev Infect Dis. 1984 Jan-Feb;6(1):51–95. doi: 10.1093/clinids/6.1.51. [DOI] [PubMed] [Google Scholar]
- Gery I., Gershon R. K., Waksman B. H. Potentiation of cultured mouse thymocyte responses by factors released by peripheral leucocytes. J Immunol. 1971 Dec;107(6):1778–1780. [PubMed] [Google Scholar]
- Kilian P. L., Kaffka K. L., Stern A. S., Woehle D., Benjamin W. R., Dechiara T. M., Gubler U., Farrar J. J., Mizel S. B., Lomedico P. T. Interleukin 1 alpha and interleukin 1 beta bind to the same receptor on T cells. J Immunol. 1986 Jun 15;136(12):4509–4514. [PubMed] [Google Scholar]
- Le P. T., Tuck D. T., Dinarello C. A., Haynes B. F., Singer K. H. Human thymic epithelial cells produce interleukin 1. J Immunol. 1987 Apr 15;138(8):2520–2526. [PubMed] [Google Scholar]
- Männel D. N., Falk W., Meltzer M. S. Inhibition of nonspecific tumoricidal activity by activated macrophages with antiserum against a soluble cytotoxic factor. Infect Immun. 1981 Jul;33(1):156–164. doi: 10.1128/iai.33.1.156-164.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pommier C. G., Inada S., Fries L. F., Takahashi T., Frank M. M., Brown E. J. Plasma fibronectin enhances phagocytosis of opsonized particles by human peripheral blood monocytes. J Exp Med. 1983 Jun 1;157(6):1844–1854. doi: 10.1084/jem.157.6.1844. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ruco L. P., Meltzer M. S. Macrophage activation for tumor cytotoxicity: development of macrophage cytotoxic activity requires completion of a sequence of short-lived intermediary reactions. J Immunol. 1978 Nov;121(5):2035–2042. [PubMed] [Google Scholar]
- Ruco L. P., Meltzer M. S. Macrophage activation for tumor cytotoxicity: induction of tumoricidal macrophages by supernatants of PPD-stimulated Bacillus Calmette-Guérin-immune spleen cell cultures. J Immunol. 1977 Sep;119(3):889–896. [PubMed] [Google Scholar]
- Schultzberg M., Svenson S. B., Unden A., Bartfai T. Interleukin-1-like immunoreactivity in peripheral tissues. J Neurosci Res. 1987;18(1):184–189. doi: 10.1002/jnr.490180126. [DOI] [PubMed] [Google Scholar]
- Shaw L. M., Mercurio A. M. Interferon gamma and lipopolysaccharide promote macrophage adherence to basement membrane glycoproteins. J Exp Med. 1989 Jan 1;169(1):303–308. doi: 10.1084/jem.169.1.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sisson S. D., Dinarello C. A. Production of interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor by human mononuclear cells stimulated with granulocyte-macrophage colony-stimulating factor. Blood. 1988 Oct;72(4):1368–1374. [PubMed] [Google Scholar]
- Takács L., Kovacs E. J., Smith M. R., Young H. A., Durum S. K. Detection of IL-1 alpha and IL-1 beta gene expression by in situ hybridization. Tissue localization of IL-1 mRNA in the normal C57BL/6 mouse. J Immunol. 1988 Nov 1;141(9):3081–3095. [PubMed] [Google Scholar]
- Tovey M. G., Content J., Gresser I., Gugenheim J., Blanchard B., Guymarho J., Poupart P., Gigou M., Shaw A., Fiers W. Genes for IFN-beta-2 (IL-6), tumor necrosis factor, and IL-1 are expressed at high levels in the organs of normal individuals. J Immunol. 1988 Nov 1;141(9):3106–3110. [PubMed] [Google Scholar]





