Abstract
The induction of lymphocyte suppressor activity with bacterial endotoxin is well documented. While most of the evidence has been obtained using animal models and has required large doses of endotoxin, we have demonstrated that additions of as little as 1.0 ng of chromatographically purified endotoxin [fromEscherichia coli 055:B5,E. coli 0111:B4,Pseudomonas aeruginosa (Fisher-Devlin immunotype 1),Serratia marcescens, orSalmonella minnesota] to human mixed lymphocyte or to mitogen-stimulated cultures produced statistically significant suppression. In each case, endotoxin was most suppressive when present in the culture system prior to the introduction of the alloantigen or mitogen. Suppressive effects were dependent upon the participation of peripheral blood monocytes and could be blocked by the addition of the prostaglandin synthetase inhibitor indomethacin or meclofenamate sodium. Prostaglandin production by monocytes appeared to induce a population of “short-lived” suppressor cells, identified by the immediate and delayed addition of lymphocyte cocultures to endotoxin-preincubated cells. The suppressive behavior of endotoxin-primed lymphocytes was identical to the behavior of burn patient serum-primed lymphocytes or to lymphocyte populations derived from a subpopulation of burn patients whose serum wasLimulus positive. We, therefore, feel that endotoxin plays a significant immunologic role in these patients.
Similar content being viewed by others
References
Nakano M, Uchiyama T, Saito K: Adjuvant effect of endotoxin: Antibody response to sheep erythrocytes in mice after transfer of syngeneic lymphoid cells treated with bacterial lipopolysaccharide in vitro. J Immunol 110:408–413, 1973
Coutinho A, Gronowitz E, Bullock WW, Moller G: Mechanism of thymus-independent immunocyte triggering. J Exp Med 139:74–92, 1974
Coutinho A, Forni L, Wetanabe T: Genetic and functional characterization of an antiserum to the lipid-A-specific triggering receptor on murine B lymphocytes. Eur J Immunol 8:63–67, 1978
Hamaoka T, Katz DH: Cellular site of action of various adjuvants in antibody response to hapten-carrier conjugates. J Immunol 111:1554–1563, 1973
Spitznagel JK, Allison AC: Mode of action of adjuvants: Effects on antibody responses to macrophage-associated bovine serum albumin. J Immunol 104:128–139, 1970
Hoffman MK, Weiss O, Koenig S, Hirst JA, Oettgen HF: Suppression an enhancement of the T cell-dependent production of antibody to SRBC in vitro by bacterial lipopolysaccharide. J Immunol 114:738–741, 1975
Unanue ER, Kiely JM, Calderon J: The modulation of lymphocyte function by molecules secreted by macrophages. II. Conditions leading to increased secretion. J Exp Med 144:155–166, 1976
Schlessinger, D: Section I. Endogenous mediators in host responses to bacterial endotoxin.In Microbiology—1980, D Schlessinger (ed). Washington, DC, American Society for Microbiology, 1980, pp 3–116
Uchiyama T, Jacobs DM: Modulation of immune response by bacterial lipopolysaccharide (LPS): Multifocal effects of LPS-induced suppression of the primary antibody response to a T-dependent antigen. J Immunol 121:2340–2346, 1978
Uchiyama T, Jacobs DM: Modulation of immune response by bacterial lipopolysaccharide (LPS) on the in vitro IgM antibody response to a T-dependent antigen. J Immunol 121:2347–2351, 1978
Diamantstein T, Keppler W, Blitstein-Willinger E, Ben-Efriam S: Suppression of the primary immune response in vivo to sheep red blood cells by B cell mitogens. Immunology 30:401–407, 1976
Cruss JM, Forbes JT, Shivers BR, Gillespie GY, Lewis GK, Scales RW: An synergistic immunosuppressive effect of endotoxin and PHA-M on immunologic enhancement in mice. Z Immun Forsch 143:31–42, 1972
Persson U: Lipopolysaccharide-induced suppression of the primary immune response to a thymus-dependent antigen. J Immunol 118:789–796, 1977
Louis JA, Lampert PH: Lipopolysaccharides: From immunostimulation to autoimmunity. Springer Semin Immunopathol 2:215–228, 1979
Lagrange PH, Mackaness GB, Miller TE, Pardon P: Effects of bacterial lipopolysaccharide on the induction and expression of cell-mediated immunity. I. Depression of the afferent arc. J Immunol 114:442–446, 1975
Lagrange PH, Mackaness GB: Effects of bacterial lipopolysaccharide on the induction and expression of cell-mediated immunity. II. Stimulation of the efferent arc. J Immunol 114:447–451, 1975
Ninnemann JL, Stein MD: Bacterial endotoxin and the generation of suppressor T cells following thermal injury. J Trauma 20:959–966, 1980
Westphal O, Jann K: Bacterial lipopolysaccharides. Extraction with phenol-water and further applications of the procedure.In Methods in Carbohydrate Chemistry, Vol V, CL Wistler (ed). New York, Academic Press, 1965, pp 83–96
Galanos C, Luderitz O, Westphal O: A new method for the extraction of R lipopolysaccharides. Eur J Biochem 9:245–249, 1969
Jondal M, Hohn G, Wigzel H: Surface markers on human T and B lymphocytes. I. A large population of lymphocytes forming nonimmune rosettes with sheep red blood cells. J Exp Med 136:207–215, 1972
Fisher JC, Wells JA, Fulwider BT: Do we need a burn severity grading system? J Trauma 17:252–255, 1977
Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature (Lond) New Biol 231:232–235, 1971
Rosenstreich DL, Vogel SN: Section I. Central role of macrophages in the host response to endotoxin.In Microbiology—1980, D Schlessinger (ed). Washington, DC, American Society for Microbiology, 1980, pp 11–15
Wilton JM, Rosenstreich DL, Oppenheim JJ: Activation of guinea pig macrophages by bacterial lipopolysaccharide requires bone marrow-derived lymphocytes. J Immunol 114:388–393, 1975
Rietschel ET, Schade U, Luderitz, O, Fischer H, Peskar BA: Section I. Prostaglandins in endotoxicosis.In Microbiology—1980, D Schlessinger (ed). Washington, DC, American Society for Microbiology, 1980, pp 66–72
Fox RA, Rajaraman K: Endotoxin and macrophage-migration inhibition. Cell Immunol 53:333–340, 1980
Kahn A, Brachet E: Involvement of prostaglandins in the local action of endotoxin. Prostagland Med 6:23–28, 1981
Fletcher JR, Ramwell PW:E. coli endotoxin shock in the baboon: Treatment with lidocaine or indomethacin.In Advances in Prostaglandin and Thromboxane Research, Vol 3, C Galli, G Galli, G Procellati (eds). New York, Raven Press, 1978, pp 183–192
Flynn JT: Endotoxin shock in the rabbit: The effects of prostaglandin and arachidonic acid administration. J Pharmacol Exp Ther 206:555–566, 1978
Ninnemann JL: Immune depression in burn and trauma patients: The role of serum borne immunosuppressive substances.In Traumatic Injury: Infection and Other Immunologic Sequelae, JL Ninnemann (ed). Baltimore, University Park Press, 1983 (in press)
Ninnemann JL, Stein MD, Condie JT: Lymphocyte response following thermal injury: The effect of circulating immunosuppressive substances. J Burn Care Rehab 2:196–199, 1981
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ninnemann, J.L., Stockland, A.E. & Condie, J.T. Induction of prostaglandin synthesis-dependent suppressor cells with endotoxin: Occurrence in patients with thermal injuries. J Clin Immunol 3, 142–150 (1983). https://doi.org/10.1007/BF00915485
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00915485