Abstract
The overproduction of cytokines such as the tumor necrosis factor-α (TNF-α) and interleukin-1α (IL-1α) may cause further deterioration in the already critical condition of patients with shock, sepsis, and acute inflammation. The effectiveness of infusion therapy of natural human IgG to such patients is suggested to depend partly upon the inhibition of the productivity of these cytokines. In this study, we investigated the modulation effects of IgG and its fragments on the production of TNF-α and IL-1α, on human peripheral blood mononuclear cells (PBMC). The production of TNF-α and IL-1α was found to be dose-dependently inhibited by IgG when stimulated by lipopolysaccharide (LPS), phytohemagglutinin (PHA), concanavalin A (Con A), and interleukin-2 (IL-2). However, no inhibition was seen when stimulated by phorbormyristate acetate (PMA). The F(ab′)2 fragment showed enhancing effects on cytokine production by LPS, while the Fc fragment showed not as much inhibitory effect as whole intact IgG. IgG showed no direct cytotoxic effect on PBMC. These data suggest that natural human IgG inhibits TNF-α and IL-1α production by PBMC through the Fc portion. The results of this study led us to conclude that whole intact IgG may be the best form of therapeutic delivery.
Similar content being viewed by others
References
Berkman SA, Lee ML, Gale RP (1988) Clinical uses of intravenous immunoglobulins. Semin Hematol 25:140–158
Barandum S, Morell A, Skvaril F (1980) Clinical use of intravenous gamma-globlin. Bibl Haemat 46:170–174
Stiehm ER, Ashida E, Kim KS, Winston DJ, Haas A, Gale RP (1987) Intravenous immunogulobulins as therapeutic agents. Ann Intern Med 107:367–382
Eskay RL, Grino M, Chen HT (1990) Interleukins, signal transduction, and immune system-mediated stress response Adv Exp Med Biol 274:331–343
Bermudez LE, Wu M, Young LS (1990) Effect of stress-related hormones on macrophage receptors and response to tumor necrosis factor Lymphokine Res 9:137–145
Abe Y, Miyake M, Horiuchi A, Kumori K, Kimura S (1992) Changes of the productivity of cytokines and active-oxygen in peripheral blood cells following surgery. Jpn J Surg 22:15–18
Brown JM, Grosso MA, Harken AH (1989) Cytokines, sepsis and the surgeon. Surg Gynecol Obstet 169:568–575
Tracey KJ, Fong Y, Hesse DG, Manogue KR, Lee AT, Kuo GC, Lowery SF, Cerami A (1987) Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteremia. Nature 330:662–664
Iwata M, Shimazato T, Tokiwa H, Tsubura E (1987) Antipyretic activity of a human immunoglobulin preparation for intravenous use in an experimental model of fever in rabbits. Infect Immunity 55:547–554
Shimazato T, Iwata M, Tamura N (1990) Suppression of tumor necrosis factor alpha by a human immunoglobulin preparation for intravenous use. Infect Immunity 58:1384–1390
Abe Y, Miyake M, Sagawa T, Kimura S (1988) Enzyme-linked immunosorbent assay (ELISA) for human tumor necrosis factor-α (hTNF-α). Clin Chim Acta 176:213–218
Abe Y, Miyake M, Horiuchi A, Sagawa T, Ono H, Kimura S (1989) Non-specific reaction in the sandwich immunoassay for tumor necrosis factor-α (hTNF-α). Clin Chim Acta 181:223–230
Jue D-M, Sherry B, Leudke C, Manogue KR, Cerami A (1990) Processing of newly synthesized cachectin/tumor necrosis factor in endotoxin-stimulated macrophages. Biochem 29:8371–8377
Abraham RT, Ho SN, Barna TJ, McKean DJ (1987) Transmembrane signaling during interleukin-1-dependent T-cell activation. Interactions of signal transduction 2-type mediators with the phosphoionositide-dependent signal transduction mechanism. J Biol Chem 262:2719–2728
Witters LA, Blackshear PJ (1987) Protein kinase C-mediated phosphorylation in intact cells. In: Conn PM, Means AR (eds) Methods in enzymology. Academic, London, p 412
Gatanaga T, Hwang C, Kohr W, Cappucini F, Lucci JA III, Jeffs EWB, Lentz R, Tomich J, Yamamoto RS, Granger GA (1990) Purification and characterization of inhibitor (soluble tumor necrosis factor receptor) for tumor necrosis factor and lymphotoxin from the serum ultrafiltrates of human cancer patients. Proc Natl Acad Sci 87:8781–8784
Engelberts I, Schoen G, Van Der Linden C, Buurman WA (1991) Evaluation of measurement of human TNF in plasma by ELISA. Lymphokine Cytokine Res 10:69–76
Gray PW, Barret K, Chantry D, Turner M, Feldmann M (1990) Cloning of human tumor necrosis factor (TNF) receptor cDNA and expression of recombinant soluble TNF-binding pretein. Proc Natl Acad Sci 87:7380–7384
Phillips NE, Parker DC (1983) Fc-dependent inhibition of mouse B cell activation by whole anti-antibodies. J Immunol 130:602–606
Phillips NE, Parker DC (1984) Cross-linking of B lymphocyte Fc-receptors and membrane immunoglobulin inhibits anti-immunoglobulin-induced blast genesis. J Immunol 132:627–632
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Horiuchi, A., Abe, Y., Miyake, M. et al. Natural human IgG inhibits the production of tumor necrosis factor-α and interleukin-1α through the Fc portion. Surg Today 23, 241–245 (1993). https://doi.org/10.1007/BF00309234
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00309234