Europe PMC

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

Abstract 


The production by monocytes of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) in intensive care unit (ICU) patients with sepsis syndrome (n = 23) or noninfectious shock (n = 6) is reported. Plasma cytokines, cell-associated cytokines within freshly isolated monocytes and LPS-induced in vitro cytokine production were assessed at admission and at regular intervals during ICU stay. TNF alpha and IL-6 were the most frequently detected circulating cytokines. Despite the fact that IL-1 alpha is the main cytokine found within monocytes upon in vitro activation of cells from healthy individuals, it was very rarely detected within freshly isolated monocytes from septic patients, and levels of cell-associated IL-1 beta were lower than those of TNF alpha. Cell-associated IL-1 beta and TNF alpha were not correlated with corresponding levels in plasma. Upon LPS stimulation, we observed a profound decrease of in vitro IL-1 alpha production by monocytes in all patients, and of IL-1 beta, IL-6, and TNF alpha in septic patients. This reduced LPS-induced production of cytokines was most pronounced in patients with gram-negative infections. Finally, monocytes from survival patients, but not from nonsurvival ones recovered their capacity to produce normal amounts of cytokines upon LPS stimulation. In conclusion, our data indicate an in vivo activation of circulating monocytes during sepsis as well as in noninfectious shock and suggest that complex regulatory mechanisms can downregulate the production of cytokines by monocytes during severe infections.

Free full text 


Logo of jcinvestThe Journal of Clinical Investigation
J Clin Invest. 1991 Nov; 88(5): 1747–1754.
PMCID: PMC295719
PMID: 1939659

Dysregulation of in vitro cytokine production by monocytes during sepsis.

Abstract

The production by monocytes of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) in intensive care unit (ICU) patients with sepsis syndrome (n = 23) or noninfectious shock (n = 6) is reported. Plasma cytokines, cell-associated cytokines within freshly isolated monocytes and LPS-induced in vitro cytokine production were assessed at admission and at regular intervals during ICU stay. TNF alpha and IL-6 were the most frequently detected circulating cytokines. Despite the fact that IL-1 alpha is the main cytokine found within monocytes upon in vitro activation of cells from healthy individuals, it was very rarely detected within freshly isolated monocytes from septic patients, and levels of cell-associated IL-1 beta were lower than those of TNF alpha. Cell-associated IL-1 beta and TNF alpha were not correlated with corresponding levels in plasma. Upon LPS stimulation, we observed a profound decrease of in vitro IL-1 alpha production by monocytes in all patients, and of IL-1 beta, IL-6, and TNF alpha in septic patients. This reduced LPS-induced production of cytokines was most pronounced in patients with gram-negative infections. Finally, monocytes from survival patients, but not from nonsurvival ones recovered their capacity to produce normal amounts of cytokines upon LPS stimulation. In conclusion, our data indicate an in vivo activation of circulating monocytes during sepsis as well as in noninfectious shock and suggest that complex regulatory mechanisms can downregulate the production of cytokines by monocytes during severe infections.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.7M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Shalaby MR, Waage A, Aarden L, Espevik T. Endotoxin, tumor necrosis factor-alpha and interleukin 1 induce interleukin 6 production in vivo. Clin Immunol Immunopathol. 1989 Dec;53(3):488–498. [Abstract] [Google Scholar]
  • Evans GF, Snyder YM, Butler LD, Zuckerman SH. Differential expression of interleukin-1 and tumor necrosis factor in murine septic shock models. Circ Shock. 1989 Dec;29(4):279–290. [Abstract] [Google Scholar]
  • Adams JL, Semrad SD, Czuprynski CJ. Administration of bacterial lipopolysaccharide elicits circulating tumor necrosis factor-alpha in neonatal calves. J Clin Microbiol. 1990 May;28(5):998–1001. [Europe PMC free article] [Abstract] [Google Scholar]
  • Fong Y, Lowry SF. Tumor necrosis factor in the pathophysiology of infection and sepsis. Clin Immunol Immunopathol. 1990 May;55(2):157–170. [Abstract] [Google Scholar]
  • LeMay DR, LeMay LG, Kluger MJ, D'Alecy LG. Plasma profiles of IL-6 and TNF with fever-inducing doses of lipopolysaccharide in dogs. Am J Physiol. 1990 Jul;259(1 Pt 2):R126–R132. [Abstract] [Google Scholar]
  • Waage A, Halstensen A, Shalaby R, Brandtzaeg P, Kierulf P, Espevik T. Local production of tumor necrosis factor alpha, interleukin 1, and interleukin 6 in meningococcal meningitis. Relation to the inflammatory response. J Exp Med. 1989 Dec 1;170(6):1859–1867. [Europe PMC free article] [Abstract] [Google Scholar]
  • Michie HR, Manogue KR, Spriggs DR, Revhaug A, O'Dwyer S, Dinarello CA, Cerami A, Wolff SM, Wilmore DW. Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med. 1988 Jun 9;318(23):1481–1486. [Abstract] [Google Scholar]
  • Fong Y, Moldawer LL, Marano M, Wei H, Tatter SB, Clarick RH, Santhanam U, Sherris D, May LT, Sehgal PB, et al. Endotoxemia elicits increased circulating beta 2-IFN/IL-6 in man. J Immunol. 1989 Apr 1;142(7):2321–2324. [Abstract] [Google Scholar]
  • Cannon JG, Tompkins RG, Gelfand JA, Michie HR, Stanford GG, van der Meer JW, Endres S, Lonnemann G, Corsetti J, Chernow B, et al. Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. J Infect Dis. 1990 Jan;161(1):79–84. [Abstract] [Google Scholar]
  • Waage A, Halstensen A, Espevik T. Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet. 1987 Feb 14;1(8529):355–357. [Abstract] [Google Scholar]
  • Girardin E, Grau GE, Dayer JM, Roux-Lombard P, Lambert PH. Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura. N Engl J Med. 1988 Aug 18;319(7):397–400. [Abstract] [Google Scholar]
  • Waage A, Brandtzaeg P, Halstensen A, Kierulf P, Espevik T. The complex pattern of cytokines in serum from patients with meningococcal septic shock. Association between interleukin 6, interleukin 1, and fatal outcome. J Exp Med. 1989 Jan 1;169(1):333–338. [Europe PMC free article] [Abstract] [Google Scholar]
  • Helfgott DC, Tatter SB, Santhanam U, Clarick RH, Bhardwaj N, May LT, Sehgal PB. Multiple forms of IFN-beta 2/IL-6 in serum and body fluids during acute bacterial infection. J Immunol. 1989 Feb 1;142(3):948–953. [Abstract] [Google Scholar]
  • Hack CE, De Groot ER, Felt-Bersma RJ, Nuijens JH, Strack Van Schijndel RJ, Eerenberg-Belmer AJ, Thijs LG, Aarden LA. Increased plasma levels of interleukin-6 in sepsis. Blood. 1989 Oct;74(5):1704–1710. [Abstract] [Google Scholar]
  • de Groote MA, Martin MA, Densen P, Pfaller MA, Wenzel RP. Plasma tumor necrosis factor levels in patients with presumed sepsis. Results in those treated with antilipid A antibody vs placebo. JAMA. 1989 Jul 14;262(2):249–251. [Abstract] [Google Scholar]
  • Calandra T, Baumgartner JD, Grau GE, Wu MM, Lambert PH, Schellekens J, Verhoef J, Glauser MP. Prognostic values of tumor necrosis factor/cachectin, interleukin-1, interferon-alpha, and interferon-gamma in the serum of patients with septic shock. Swiss-Dutch J5 Immunoglobulin Study Group. J Infect Dis. 1990 May;161(5):982–987. [Abstract] [Google Scholar]
  • Marks JD, Marks CB, Luce JM, Montgomery AB, Turner J, Metz CA, Murray JF. Plasma tumor necrosis factor in patients with septic shock. Mortality rate, incidence of adult respiratory distress syndrome, and effects of methylprednisolone administration. Am Rev Respir Dis. 1990 Jan;141(1):94–97. [Abstract] [Google Scholar]
  • Marano MA, Fong Y, Moldawer LL, Wei H, Calvano SE, Tracey KJ, Barie PS, Manogue K, Cerami A, Shires GT, et al. Serum cachectin/tumor necrosis factor in critically ill patients with burns correlates with infection and mortality. Surg Gynecol Obstet. 1990 Jan;170(1):32–38. [Abstract] [Google Scholar]
  • Goldblum SE, Yoneda K, Cohen DA, McClain CJ. Provocation of pulmonary vascular endothelial injury in rabbits by human recombinant interleukin-1 beta. Infect Immun. 1988 Sep;56(9):2255–2263. [Europe PMC free article] [Abstract] [Google Scholar]
  • Stephens KE, Ishizaka A, Wu ZH, Larrick JW, Raffin TA. Granulocyte depletion prevents tumor necrosis factor-mediated acute lung injury in guinea pigs. Am Rev Respir Dis. 1988 Nov;138(5):1300–1307. [Abstract] [Google Scholar]
  • Jacobs RF, Tabor DR, Burks AW, Campbell GD. Elevated interleukin-1 release by human alveolar macrophages during the adult respiratory distress syndrome. Am Rev Respir Dis. 1989 Dec;140(6):1686–1692. [Abstract] [Google Scholar]
  • Ferrari-Baliviera E, Mealy K, Smith RJ, Wilmore DW. Tumor necrosis factor induces adult respiratory distress syndrome in rats. Arch Surg. 1989 Dec;124(12):1400–1405. [Abstract] [Google Scholar]
  • Okusawa S, Gelfand JA, Ikejima T, Connolly RJ, Dinarello CA. Interleukin 1 induces a shock-like state in rabbits. Synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition. J Clin Invest. 1988 Apr;81(4):1162–1172. [Europe PMC free article] [Abstract] [Google Scholar]
  • Dunn CJ, Schaub RG, Fleming WE, Gibbons AJ. Interleukin-1 induced vascular pathology "in vivo": a scanning electron-microscopy study. Agents Actions. 1989 Jun;27(3-4):287–289. [Abstract] [Google Scholar]
  • Natanson C, Eichenholz PW, Danner RL, Eichacker PQ, Hoffman WD, Kuo GC, Banks SM, MacVittie TJ, Parrillo JE. Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock. J Exp Med. 1989 Mar 1;169(3):823–832. [Europe PMC free article] [Abstract] [Google Scholar]
  • Bevilacqua MP, Pober JS, Majeau GR, Fiers W, Cotran RS, Gimbrone MA., Jr Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin 1. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4533–4537. [Europe PMC free article] [Abstract] [Google Scholar]
  • van der Poll T, Büller HR, ten Cate H, Wortel CH, Bauer KA, van Deventer SJ, Hack CE, Sauerwein HP, Rosenberg RD, ten Cate JW. Activation of coagulation after administration of tumor necrosis factor to normal subjects. N Engl J Med. 1990 Jun 7;322(23):1622–1627. [Abstract] [Google Scholar]
  • Cybulsky MI, Movat HZ, Dinarello CA. Role of interleukin-1 and tumour necrosis factor-alpha in acute inflammation. Ann Inst Pasteur Immunol. 1987 May-Jun;138(3):505–512. [Abstract] [Google Scholar]
  • Saukkonen K, Sande S, Cioffe C, Wolpe S, Sherry B, Cerami A, Tuomanen E. The role of cytokines in the generation of inflammation and tissue damage in experimental gram-positive meningitis. J Exp Med. 1990 Feb 1;171(2):439–448. [Europe PMC free article] [Abstract] [Google Scholar]
  • Gauldie J, Richards C, Harnish D, Lansdorp P, Baumann H. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7251–7255. [Europe PMC free article] [Abstract] [Google Scholar]
  • Ramadori G, Van Damme J, Rieder H, Meyer zum Büschenfelde KH. Interleukin 6, the third mediator of acute-phase reaction, modulates hepatic protein synthesis in human and mouse. Comparison with interleukin 1 beta and tumor necrosis factor-alpha. Eur J Immunol. 1988 Aug;18(8):1259–1264. [Abstract] [Google Scholar]
  • Gauldie J, Northemann W, Fey GH. IL-6 functions as an exocrine hormone in inflammation. Hepatocytes undergoing acute phase responses require exogenous IL-6. J Immunol. 1990 May 15;144(10):3804–3808. [Abstract] [Google Scholar]
  • Opp M, Obal F, Jr, Cady AB, Johannsen L, Krueger JM. Interleukin-6 is pyrogenic but not somnogenic. Physiol Behav. 1989 May;45(5):1069–1072. [Abstract] [Google Scholar]
  • LeMay LG, Otterness IG, Vander AJ, Kluger MJ. In vivo evidence that the rise in plasma IL 6 following injection of a fever-inducing dose of LPS is mediated by IL 1 beta. Cytokine. 1990 May;2(3):199–204. [Abstract] [Google Scholar]
  • Jablons DM, Mulé JJ, McIntosh JK, Sehgal PB, May LT, Huang CM, Rosenberg SA, Lotze MT. IL-6/IFN-beta-2 as a circulating hormone. Induction by cytokine administration in humans. J Immunol. 1989 Mar 1;142(5):1542–1547. [Abstract] [Google Scholar]
  • Brouckaert P, Spriggs DR, Demetri G, Kufe DW, Fiers W. Circulating interleukin 6 during a continuous infusion of tumor necrosis factor and interferon gamma. J Exp Med. 1989 Jun 1;169(6):2257–2262. [Europe PMC free article] [Abstract] [Google Scholar]
  • De Simoni MG, Sironi M, De Luigi A, Manfridi A, Mantovani A, Ghezzi P. Intracerebroventricular injection of interleukin 1 induces high circulating levels of interleukin 6. J Exp Med. 1990 May 1;171(5):1773–1778. [Europe PMC free article] [Abstract] [Google Scholar]
  • Smith DM, Lackides GA, Epstein LB. Coordinated induction of autocrine tumor necrosis factor and interleukin 1 in normal human monocytes and the implications for monocyte-mediated cytotoxicity. Cancer Res. 1990 Jun 1;50(11):3146–3153. [Abstract] [Google Scholar]
  • Ikejima T, Okusawa S, Ghezzi P, van der Meer JW, Dinarello CA. Interleukin-1 induces tumor necrosis factor (TNF) in human peripheral blood mononuclear cells in vitro and a circulating TNF-like activity in rabbits. J Infect Dis. 1990 Jul;162(1):215–223. [Abstract] [Google Scholar]
  • Movat HZ, Burrowes CE, Cybulsky MI, Dinarello CA. Acute inflammation and a Shwartzman-like reaction induced by interleukin-1 and tumor necrosis factor. Synergistic action of the cytokines in the induction of inflammation and microvascular injury. Am J Pathol. 1987 Dec;129(3):463–476. [Europe PMC free article] [Abstract] [Google Scholar]
  • Baumann H, Richards C, Gauldie J. Interaction among hepatocyte-stimulating factors, interleukin 1, and glucocorticoids for regulation of acute phase plasma proteins in human hepatoma (HepG2) cells. J Immunol. 1987 Dec 15;139(12):4122–4128. [Abstract] [Google Scholar]
  • Last-Barney K, Homon CA, Faanes RB, Merluzzi VJ. Synergistic and overlapping activities of tumor necrosis factor-alpha and IL-1. J Immunol. 1988 Jul 15;141(2):527–530. [Abstract] [Google Scholar]
  • Andus T, Geiger T, Hirano T, Kishimoto T, Heinrich PC. Action of recombinant human interleukin 6, interleukin 1 beta and tumor necrosis factor alpha on the mRNA induction of acute-phase proteins. Eur J Immunol. 1988 May;18(5):739–746. [Abstract] [Google Scholar]
  • Rothstein JL, Schreiber H. Synergy between tumor necrosis factor and bacterial products causes hemorrhagic necrosis and lethal shock in normal mice. Proc Natl Acad Sci U S A. 1988 Jan;85(2):607–611. [Europe PMC free article] [Abstract] [Google Scholar]
  • Haeffner-Cavaillon N, Cavaillon JM, Ciancioni C, Bacle F, Delons S, Kazatchkine MD. In vivo induction of interleukin-1 during hemodialysis. Kidney Int. 1989 May;35(5):1212–1218. [Abstract] [Google Scholar]
  • Haeffner-Cavaillon N, Roussellier N, Ponzio O, Carreno MP, Laude M, Carpentier A, Kazatchkine MD. Induction of interleukin-1 production in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1989 Dec;98(6):1100–1106. [Abstract] [Google Scholar]
  • Bone RC, Fisher CJ, Jr, Clemmer TP, Slotman GJ, Metz CA, Balk RA. Sepsis syndrome: a valid clinical entity. Methylprednisolone Severe Sepsis Study Group. Crit Care Med. 1989 May;17(5):389–393. [Abstract] [Google Scholar]
  • Le Gall JR, Loirat P, Alperovitch A, Glaser P, Granthil C, Mathieu D, Mercier P, Thomas R, Villers D. A simplified acute physiology score for ICU patients. Crit Care Med. 1984 Nov;12(11):975–977. [Abstract] [Google Scholar]
  • Tucker SB, Pierre RV, Jordon RE. Rapid identification of monocytes in a mixed mononuclear cell preparation. J Immunol Methods. 1977;14(3-4):267–269. [Abstract] [Google Scholar]
  • Cavaillon JM, Fitting C, Haeffner-Cavaillon N. Recombinant C5a enhances interleukin 1 and tumor necrosis factor release by lipopolysaccharide-stimulated monocytes and macrophages. Eur J Immunol. 1990 Feb;20(2):253–257. [Abstract] [Google Scholar]
  • Cavaillon JM, Fitting C, Haeffner-Cavaillon N, Kirsch SJ, Warren HS. Cytokine response by monocytes and macrophages to free and lipoprotein-bound lipopolysaccharide. Infect Immun. 1990 Jul;58(7):2375–2382. [Europe PMC free article] [Abstract] [Google Scholar]
  • Van Snick J, Cayphas S, Vink A, Uyttenhove C, Coulie PG, Rubira MR, Simpson RJ. Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9679–9683. [Europe PMC free article] [Abstract] [Google Scholar]
  • Hansen MB, Nielsen SE, Berg K. Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods. 1989 May 12;119(2):203–210. [Abstract] [Google Scholar]
  • van der Meer JW, Endres S, Lonnemann G, Cannon JG, Ikejima T, Okusawa S, Gelfand JA, Dinarello CA. Concentrations of immunoreactive human tumor necrosis factor alpha produced by human mononuclear cells in vitro. J Leukoc Biol. 1988 Mar;43(3):216–223. [Abstract] [Google Scholar]
  • Cannon JG, van der Meer JW, Kwiatkowski D, Endres S, Lonnemann G, Burke JF, Dinarello CA. Interleukin-1 beta in human plasma: optimization of blood collection, plasma extraction, and radioimmunoassay methods. Lymphokine Res. 1988 Winter;7(4):457–467. [Abstract] [Google Scholar]
  • Kearney JF, Radbruch A, Liesegang B, Rajewsky K. A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J Immunol. 1979 Oct;123(4):1548–1550. [Abstract] [Google Scholar]
  • Beutler BA, Milsark IW, Cerami A. Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo. J Immunol. 1985 Dec;135(6):3972–3977. [Abstract] [Google Scholar]
  • Klapproth J, Castell J, Geiger T, Andus T, Heinrich PC. Fate and biological action of human recombinant interleukin 1 beta in the rat in vivo. Eur J Immunol. 1989 Aug;19(8):1485–1490. [Abstract] [Google Scholar]
  • Castell JV, Geiger T, Gross V, Andus T, Walter E, Hirano T, Kishimoto T, Heinrich PC. Plasma clearance, organ distribution and target cells of interleukin-6/hepatocyte-stimulating factor in the rat. Eur J Biochem. 1988 Nov 1;177(2):357–361. [Abstract] [Google Scholar]
  • Munoz C, Misset B, Fitting C, Blériot JP, Carlet J, Cavaillon JM. Dissociation between plasma and monocyte-associated cytokines during sepsis. Eur J Immunol. 1991 Sep;21(9):2177–2184. [Abstract] [Google Scholar]
  • Offner F, Philippé J, Vogelaers D, Colardyn F, Baele G, Baudrihaye M, Vermeulen A, Leroux-Roels G. Serum tumor necrosis factor levels in patients with infectious disease and septic shock. J Lab Clin Med. 1990 Jul;116(1):100–105. [Abstract] [Google Scholar]
  • Endres S, Cannon JG, Ghorbani R, Dempsey RA, Sisson SD, Lonnemann G, Van der Meer JW, Wolff SM, Dinarello CA. In vitro production of IL 1 beta, IL 1 alpha, TNF and IL2 in healthy subjects: distribution, effect of cyclooxygenase inhibition and evidence of independent gene regulation. Eur J Immunol. 1989 Dec;19(12):2327–2333. [Abstract] [Google Scholar]
  • Cavaillon JM, Haeffner-Cavaillon N. Signals involved in interleukin 1 synthesis and release by lipopolysaccharide-stimulated monocytes/macrophages. Cytokine. 1990 Sep;2(5):313–329. [Abstract] [Google Scholar]
  • Bailly S, Mahe Y, Ferrua B, Fay M, Tursz T, Wakasugi H, Gougerot-Pocidalo MA. Quinolone-induced differential modification of IL-1 alpha and IL-1 beta production by LPS-stimulated human monocytes. Cell Immunol. 1990 Jun;128(1):277–288. [Abstract] [Google Scholar]
  • Helminen M, Vesikari T. Interleukin-1 production in bacterial meningitis. Scand J Infect Dis. 1990;22(1):105–108. [Abstract] [Google Scholar]
  • Fieren MW, Van den Bemd GJ, Bonta IL. Endotoxin-stimulated peritoneal macrophages obtained from continuous ambulatory peritoneal dialysis patients show an increased capacity to release interleukin-1 beta in vitro during infectious peritonitis. Eur J Clin Invest. 1990 Aug;20(4):453–457. [Abstract] [Google Scholar]
  • Mathison JC, Virca GD, Wolfson E, Tobias PS, Glaser K, Ulevitch RJ. Adaptation to bacterial lipopolysaccharide controls lipopolysaccharide-induced tumor necrosis factor production in rabbit macrophages. J Clin Invest. 1990 Apr;85(4):1108–1118. [Europe PMC free article] [Abstract] [Google Scholar]
  • Sanchez-Cantu L, Rode HN, Christou NV. Endotoxin tolerance is associated with reduced secretion of tumor necrosis factor. Arch Surg. 1989 Dec;124(12):1432–1436. [Abstract] [Google Scholar]
  • Haas JG, Thiel C, Blömer K, Weiss EH, Riethmüller G, Ziegler-Heitbrock HW. Downregulation of tumor necrosis factor expression in the human Mono-Mac-6 cell line by lipopolysaccharide. J Leukoc Biol. 1989 Jul;46(1):11–14. [Abstract] [Google Scholar]
  • Takayama TK, Miller C, Szabo G. Elevated tumor necrosis factor alpha production concomitant to elevated prostaglandin E2 production by trauma patients' monocytes. Arch Surg. 1990 Jan;125(1):29–35. [Abstract] [Google Scholar]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

Citations & impact 


Impact metrics

Jump to Citations

Citations of article over time

Alternative metrics

Altmetric item for https://www.altmetric.com/details/76460714
Altmetric
Discover the attention surrounding your research
https://www.altmetric.com/details/76460714

Article citations


Go to all (427) article citations