Advertisement

Immunologic Research

, Volume 20, Issue 1, pp 15–27 | Cite as

Role of cytokines in pulmonary antimicrobial host defense

  • Borna Mehrad
  • Theodore J. Standiford
Article

Abstract

Host defense of the lung is characterized by a fine balance between the generation of a vigorous inflammatory response to clear pathogens and maintenance of the integrity of the alveolar gas-exchange surface. The magnitude of the inflammatory response is therefore tightly regulated by pro- and anti-inflammatory cytokine mediators. This article summarizes current information on the roles of specific cytokines in pneumonia, with particular emphasis on ongoing investigations into the role of innate immunity in bacterial and fungal pneumonia.

Key Words

Infectious immunity Cytokines Chemokines Immunotherapy Pneumonia Lung 

Abbreviations

CLP

cecal ligation and puncture

G-CSF

granulocyte colonystimulating factor

GM-CSF

granulocyte/macrophage colonystimulating factor

IFN-γ

interferon-γ

IL-lΒ

interleukin-lΒ

IL-6

interleukin-6

IL-8

interleukin-8

IL-10

interleukin-10

IL-12

interleukin-12

LPS

lipopolysaccharide

MCP-1

monocyte chemoattractant protein-1

MlP-lα

macrophage inflammatory protein-1 α

MIP-1Β

macrophage inflammatory protein-1Β

MIP-2

macrophage inflammatory protein-2

PDGF

platelet-derived growth factor

r

recombinant

RANTES

regulated upon activation in normal T cells expressed and secreted

TGF-Β

transforming growth factor-Β

TNF

tumor necrosis factor-α

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Murray JF: The Normal Lung: The Basis for Diagnosis and Treatment of Pulmonary Disease. Philadelphia, Saunders, 1986.Google Scholar
  2. 2.
    Garibaldi RA: Epidemiology of community-acquired respiratory tract infections in adults. Incidence, etiology, and impact. Am J Med 1985;78:32–37.PubMedCrossRefGoogle Scholar
  3. 3.
    Anonymous. Statistical Abstract of the United States. Washington DC, U. S. Department of Commerce, Bureau of Census, 1988.Google Scholar
  4. 4.
    Pinner RW, Teutsch SM, Simonsen L, Klug LA, Graber JM, Clarke MJ, et al.: Trends in infectious diseases mortality in the United States. JAMA 1996;275:189–193.PubMedCrossRefGoogle Scholar
  5. 5.
    Holmberg SD, Solomon SL, Blake PA: Health and economic impacts of antimicrobial resistance. Rev Infect Dis 1987;9:1065–1078.PubMedGoogle Scholar
  6. 6.
    Reynolds HY: Normal and defective respiratory host defences; in Pennington, JE (ed): Respiratory Infections—Diagnosis and Management. New York, Raven Press, 1994, pp 1–34.Google Scholar
  7. 7.
    Jackson AE, Southern PM, Pierce AK, Fallis BD, Sanford JP: Pulmonary clearance of gram-negative bacilli. J Lab Clin Med 1967; 69:833–841.PubMedGoogle Scholar
  8. 8.
    Toews GB: Pulmonary clearance of infectious agents; inPennington, JE (ed): Respiratory Infections-Diagnosis and Managment. New York, Raven, 1994, pp 43–53.Google Scholar
  9. 9.
    Le J, Vilcek J: Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest 1987;56: 234–248.PubMedGoogle Scholar
  10. 10.
    Beutler B: TNF, immunity and inflammatory disease: lessons of the past decade. J Invest Med 1995;43:227–235.Google Scholar
  11. 11.
    Tan AM, Ferrante A, Goh DH, Roberton DM, Cripps AW: Activation of the neutrophil bactericidal activity for nontypable Haemophilus influenzae by tumor necrosis factor and lymphotoxin. PediatrRes 1995;37:155–159.Google Scholar
  12. 12.
    Oswald IP, Wynn TA, Sher A, James SL: Interleukin 10 inhibits macrophage microbicidal activity by blocking the endogenous production of tumor necrosis factor alpha required as a costimulatory factor for interferon gamma-induced activation. Proc Natl Acad Sci USA 1992;89:8676–8680.PubMedCrossRefGoogle Scholar
  13. 13.
    Huffnagle GB, Toews GB, Burdick MD, Boyd MB, McAllister KS, McDonald RA, et al.: Afferent phase production of TNF-alpha is required for the development of protective T cell immunity to Cryptococcus neoformans. J Immunol 1996;157:4529–4536.PubMedGoogle Scholar
  14. 14.
    Dehoux MS, Boutten A, Ostinelli J, Seta N, Dombret MC, Crestani B, et al.: Compartmentalized cytokine production within the human lung in unilateral pneumonia. Am J Respir Crit Care Med 1994;150: 710–716.PubMedGoogle Scholar
  15. 15.
    van der Poll T, Keogh CV, Buurman WA, Lowry SF: Passive immunization against tumor necrosis factor -alpha impairs host defense during pneumococcal pneumonia in mice. Am J Respir Crit Care Med 1997; 155:603–608.PubMedGoogle Scholar
  16. 16.
    Takashima K, Tateda K, Matsumoto T, Iizawa Y, Nakao M, Yamaguchi K: Role of tumor necrosis factor alpha in pathogenesis of pneumococcal pneumonia in mice. Infect Immun 1997;65:257–260.PubMedGoogle Scholar
  17. 17.
    Laichalk LL, Kunkel SL, Strieter RM, Danforth JM, Bailie MB, Standiford TJ: Tumor necrosis factor mediates lung antibacterial host defense in murineKlebsiella pneumonia. Infect Immun 1996; 64:5211–5218.PubMedGoogle Scholar
  18. 18.
    Gosselin D, DeSanctis J, Boule M, Skamene E, Matouk C, Radzioch D: Role of tumor necrosis factor alpha in innate resistance to mouse pulmonary infection with Pseudomonas aeruginosa. Infect Immun 1995;63:3272–3278.PubMedGoogle Scholar
  19. 19.
    Brieland JK, Remick DG, Freeman PT, Hurley MC, Fantone JC, Engleberg NC: In vivo regulation of replicative Legionella pneumophila lung infection by endogenous tumor necrosis factor alpha and nitric oxide. Infect Immun 1995;63:3253–3258.PubMedGoogle Scholar
  20. 20.
    Mehrad B, Strieter RM, Standiford TJ: Role of TNF in pulmonary host defense in murine invasive asper-gillosis. J Immunol 1999; 162: 1633–1640PubMedGoogle Scholar
  21. 21.
    Kolls JK, Beck JM, Nelson S, Summer WR, Shellito J: Alveolar macrophage release of tumor necrosis factor during murine Pneumocystis carinii pneumonia. Am J Respir Cell Mol Biol 1993; 8:370–376.PubMedGoogle Scholar
  22. 22.
    Standiford TJ, Wilkowski JM, Sisson TH, Hattori N, Mehrad B, Bucknell KA, Moore TA: Intrapulmonary tumor necrosis factor gene therapy increases bacterial clearance and survival in murine gram-negative pneumonia. Hum Gene Ther 1999; 10:899–909PubMedCrossRefGoogle Scholar
  23. 23.
    Laichalk LL, Bucknell KA, Huffnagle GB, Wilkowski JM, Moore TA, Romanelli RJ, et al.: Intrapulmonary delivery of tumor necrosis factor agonist peptide augments host defense in murine gram-negative bacterial pneumonia. Infect Immun 1998;66:2822–2826.PubMedGoogle Scholar
  24. 24.
    Standiford TJ, Kunkel SL, Greenberger MJ, Laichalk LL, Strieter RM: Expression and regulation of chemokines in bacterial pneumonia. J Leukoc Biol 1996; 59:24–28.PubMedGoogle Scholar
  25. 25.
    Huffnagle GB, Strieter RM, Kunkel SL, Toews GB, Standiford TJ: The role of chemokines in pneumonia; in Koch, A, Strieter, RM (eds): Chemokines in Disease. Austin, R.G.Landes, 1996, pp 151–168.Google Scholar
  26. 26.
    Strieter RM, Kunkel SL: Chemokines; in Crystal, RG, West, JB, Weibel, ER, Barnes, PJ (eds): The Lung: Scientific Foundations. Philadelphia, Lippincott-Raven, 1996, pp 155–186.Google Scholar
  27. 27.
    Baggiolini M, Dewald B, Moser B: Human chemokines: an update. Annu Rev Immunol 1997;15: 675–705.PubMedCrossRefGoogle Scholar
  28. 28.
    Rodriguez JL, Miller CG, DeForge LE, Kelty L, Shanley CJ, Bartlett RH, et al.: Local production of interleukin-8 is associated with nosocomial pneumonia. J Trauma 1992;33:74–81; discussion 81–72.PubMedCrossRefGoogle Scholar
  29. 29.
    Benfield TL, Vestbo J, Junge J, Nielsen TL, Jensen AB, Lundgren JD: Prognostic value of interleukin-8 in AIDS-associated Pneumocystis carinii pneumonia. Am J Respir Crit Care Med 1995; 151: 1058–1062.PubMedGoogle Scholar
  30. 30.
    Johnson MC, 2nd, Kajikawa O, Goodman RB, Wong VA, Mongovin SM, Wong WB, et al.: Molecular expression of the alpha-chemokine rabbit GRO inEscherichia coli and characterization of its production by lung cells in vitro and in vivo. J Biol Chem 1996;271: 10,853–10,858.Google Scholar
  31. 31.
    Kooguchi K, Hashimoto S, Kobayashi A, Kitamura Y, Kudoh I, Wiener-Kronish J, et al.: Role of alveolar macrophages in initiation and regulation of inflammation inPseudomonas aeruginosa pneumonia. Infect Immun 1998;66: 3164–3169.PubMedGoogle Scholar
  32. 32.
    Greenberger MJ, Strieter RM, Kunkel SL, Danforth JM, Laichalk LL, McGillicuddy DC, et al.: Neutralization of macrophage inflammatory protein-2 attenuates neutro-phil recruitment and bacterial clearance in murine Klebsiella pneumonia. J Infect Dis 1996;173:159–165.PubMedGoogle Scholar
  33. 33.
    Tsai WC, Strieter RM, Wilkowski JM, Bucknell KA, Burdick MD, Lira S A, et al.:Lung-specific transgenic expression of KC enhances resistance to Klebsiella pneumoniae in mice. J Immunol 1998; 161:2435–2440.PubMedGoogle Scholar
  34. 34.
    Gao JL, Wynn TA, Chang Y, Lee EJ, Broxraeyer HE, Cooper S, et al.: Impaired host defense, hematopoiesis, granulomatous inflammation and type 1 -type 2 cytokine balance in mice lacking CC chemokine receptor 1. J Exp Med 1997; 185:1959–1968.PubMedCrossRefGoogle Scholar
  35. 35.
    Huffnagle GB, Strieter RM, Standiford TJ, McDonald RA, Burdick MD, et al.: The role of monocyte chemotactic protein-1 (MCP-1) in the recruitment of monocytes and CD4+ T cells during a pulmonaryCryptococcus neoformans infection. J Immunol 1995;155:4790–4797.PubMedGoogle Scholar
  36. 36.
    Huffnagle GB, Strieter RM, McNeil LK, McDonald RA, Burdick MD, Kunkel SL, et al.: Macrophage inflammatory protein-1 alpha (MIP-1 alpha) is required for the efferent phase of pulmonary cell-mediated immunity to a Cryptococcus neoformans infection. J Immunol 1997; 159:318–327.PubMedGoogle Scholar
  37. 37.
    Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL: Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986;136:2348–2357.PubMedGoogle Scholar
  38. 38.
    Romagnani S: Biology of human TH1 and TH2 cells. J Clin Immunol 1995;15:121–129.PubMedCrossRefGoogle Scholar
  39. 39.
    Allen JE, Maizels RM: Thl-Th2: reliable paradigm or dangerous dogma? Immunol Today 1997;18: 387–392.PubMedCrossRefGoogle Scholar
  40. 40.
    Billiau A: Interferon-gamma: biology and role in pathogenesis. Adv Immunol 1996;62:61–130.PubMedGoogle Scholar
  41. 41.
    Boehm U, Klamp T, Groot M, Howard JC: Cellular responses to interferon-gamma. Annu Rev Immunol 1997;15:749–795.PubMedCrossRefGoogle Scholar
  42. 42.
    Gallin JI, Farber JM, Holland SM, Nutman TB: Interferon-gamma in the management of infectious diseases. Ann Intern Med 1995;123: 216–224.PubMedGoogle Scholar
  43. 43.
    The International Chronic Granulomatous Disease Cooperative Study Group. A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease. N Engl J Med 1991;324: 509–516.CrossRefGoogle Scholar
  44. 44.
    Kolls JK, Nelson S, Summer WR: Recombinant cytokines and pulmonary host defense. Am J Med Sci 1993;306:330–335.PubMedCrossRefGoogle Scholar
  45. 45.
    Appelberg R: Protective role of interferon gamma, tumor necrosis factor alpha and interleukin-6 inMycobacterium tuberculosis andM. avium infections. Immunobiology 1994;191:520–525.PubMedGoogle Scholar
  46. 46.
    Lovchik JA, Lyons CR, Lipscomb MF: A role for gamma interferoninduced nitric oxide in pulmonary clearance ofCryptococcus neoformans. Am J Respir Cell Mol Biol 1995;13:116–124.PubMedGoogle Scholar
  47. 47.
    Hoag KA, Street NE, Huffnagle GB, Lipscomb MF: Early cytokine production in pulmonaryCryptococcus neoformans infections distinguishes susceptible and resistant mice. Am J Respir Cell Mol Biol 1995;13:487–495.PubMedGoogle Scholar
  48. 48.
    Garvy BA, Ezekowitz RA, Harmsen AG: Role of gamma interferon in the host immune and inflammatory responses toPneumocystis carinii infection. Infect Immun 1997;65:373–379.PubMedGoogle Scholar
  49. 49.
    Beck JM, Liggitt HD, Brunette EN, Fuchs HJ, Shellito JE, Debs RJ: Reduction in intensity ofPneumocystis carinii pneumonia in mice by aerosol administration of gamma interferon. Infect Immun 1991;59:3859–3862.PubMedGoogle Scholar
  50. 50.
    Skerrett SJ, Martin TR: Intratracheal interferon-gamma augments pulmonary defenses in experimental legionellosis. Am J Respir Crit Care Med 1994;149:50–58.PubMedGoogle Scholar
  51. 51.
    Tsai WC, Strieter RM, Zisman DA, Wilkowski JM, Bucknell KA, Chen GH, et al.: Nitric oxide is required for effective innate immunity against Klebsiella pneumoniae. Infect Immun 1997; 65: 1870–1875.PubMedGoogle Scholar
  52. 52.
    Zisman DA, Strieter RM, Kunkel SL, Tsai WC, Wilkowski JM, Bucknell KA, et al.: Ethanol feeding impairs innate immunity and alters the expression of Thland Th2-phenotype cytokines in murineKlebsiella pneumonia. Alcohol Clin Exp Res 1998;22: 621–627.PubMedCrossRefGoogle Scholar
  53. 53.
    Greenberger MJ, Kunkel SL, Strieter RM, Lukacs NW, Bramson J, Gauldie J, et al.: IL-12 gene therapy protects mice in lethalKlebsiella pneumonia. J Immunol 1996;157:3006–3012.PubMedGoogle Scholar
  54. 54.
    Rubins JB, Pomeroy C: Role of gamma interferon in the pathogenesis of bacteremic pneumococcal pneumonia. Infect Immun 1997; 65:2975–2977.PubMedGoogle Scholar
  55. 55.
    Johansen HK, Hougen HP, Rygaard J, Hoiby N: Interferon-gamma (IFN-gamma) treatment decreases the inflammatory response in chronicPseudomonas aeruginosa pneumonia in rats. Clin Exp Immunol 1996;103:212–218.PubMedCrossRefGoogle Scholar
  56. 56.
    Kolls JK, Lei D, Nelson S, Summer WR, Shellito JE: Pulmonary cytokine gene therapy. Adenoviral -mediated murine interferon gene transfer compartmentally activates alveolar macrophages and enhances bacterial clearance. Chest 1997;111:104S.PubMedGoogle Scholar
  57. 57.
    Kolls JK, Lei D, Stoltz D, Zhang P, Schwarzenberger PO, Ye P, et al:. Adenoviral-mediated interferon -gamma gene therapy augments pulmonary host defense of ethanol-treated rats. Alcohol Clin Exp Res 1998;22:157–162.PubMedGoogle Scholar
  58. 58.
    Trinchieri G, Gerosa F: Immunoregulation by interleukin-12. J LeukocBiol 1996;59:505–511.Google Scholar
  59. 59.
    Gazzinelli RT, Hieny S, Wynn TA, Wolf S, Sher A: Interleukin 12 is required for the T-lymphocyte -independent induction of interferon gamma by an intracellular parasite and induces resistance in T cell-deficient hosts [see comments]. Proc Natl Acad Sci USA 1993:90:6115–6119.PubMedCrossRefGoogle Scholar
  60. 60.
    Heinzel FP, Schoenhaut DS, Rerko RM, Rosser LE, Gately MK: Recombinant interleukin 12 cures mice infected withLeishmania major. J Exp Med 1993; 177: 1505–1509.PubMedCrossRefGoogle Scholar
  61. 61.
    Flynn JL, Goldstein MM, Triebold KJ, Sypek J, Wolf S, Bloom BR: IL-12 increases resistance of BALB/ c mice toMycobacterium tuberculosis infection. J Immunol 1995; 155:2515–2524.PubMedGoogle Scholar
  62. 62.
    Stevenson MM, Tam MF, Wolf SF, Sher A: IL-12-induced protection against blood-stage Plasmodium chabaudi AS requires IFN-gamma and TNF-alpha and occurs via a nitric oxide-dependent mechanism. J Immunol 1995 ; 155:2545–2556.PubMedGoogle Scholar
  63. 63.
    Wagner RD, Steinberg H, Brown JF, Czuprynski CJ: Recombinant interleukin-12 enhances resistance of mice to Listeria monocytogenes infection. Microb Pathog 1994;17:175–186.PubMedCrossRefGoogle Scholar
  64. 64.
    Cooper AM, Roberts AD, Rhoades ER, Callahan JE, Getzy DM, Orme IM: The role of interleukin-12 in acquired immunity to Mycobacterium tuberculosis infection. Immunology 1995;84:423–432.PubMedGoogle Scholar
  65. 65.
    Zhou P, Sieve MC, Bennett J, Kwon-Chung KJ, Tewari RP, Gazzinelli RT, et al:. IL-12 prevents mortality in mice infected with Histoplasma capsulatum through induction of IFN-gamma. J Immunol 1995;155:785–795.PubMedGoogle Scholar
  66. 66.
    Kawakami K, Tohyama M, Xie Q, Saito A: IL-12 protects mice against pulmonary and disseminated infection caused byCryptococcus neoformans. Clin Exp Immunol 1996;104:208–214.PubMedCrossRefGoogle Scholar
  67. 67.
    Romani L, Puccetti P, Bistoni F: Interleukin-12 in infectious diseases. Clin Microbiol Rev 1997; 10:611–636.PubMedGoogle Scholar
  68. 68.
    Laichalk LL, Danforth JM, Standiford TJ: Interleukin-10 inhibits neutrophil phagocytic and bactericidal activity. FEMS Immunol Med Microbiol 1996; 15:181–187.PubMedCrossRefGoogle Scholar
  69. 69.
    Ralph P, Nakoinz I, Sampson-Johannes A, Fong S, Lowe D, et al.: IL-10, T lymphocyte inhibitor of human blood cell production of IL-1 and tumor necrosis factor. J Immunol 1992;148:808–814.PubMedGoogle Scholar
  70. 70.
    Cassatella MA, Meda L, Bonora S, Ceska M, Constantin G: Interleukin 10 (IL-10) inhibits the release of proinflammatory cytokines from human polymorphonuclear leukocytes. Evidence for an autocrine role of tumor necrosis factor and IL-1 beta in mediating the production of IL-8 triggered by lipopolysaccharide. J Exp Med 1993;178:2207–2211.PubMedCrossRefGoogle Scholar
  71. 71.
    Kasama T, Strieter RM, Lukacs NW, Burdick MD, Kunkel SL: Regulation of neutrophil-derived chemokine expression by IL-10. J Immunol 1994;152:3559–3569.PubMedGoogle Scholar
  72. 72.
    de Vries JE: Immunosuppressive and anti-inflammatory properties of interleukin 10. Ann Med 1995; 27:537–541.PubMedCrossRefGoogle Scholar
  73. 73.
    Howard M, Muchamuel T, Andrade S, Menon S: Interleukin 10 protects mice from lethal endotoxemia. J Exp Med 1993;177:1205–1208.PubMedCrossRefGoogle Scholar
  74. 74.
    Standiford TJ, Strieter RM, Lukacs NW, Kunkel SL: Neutralization of IL-10 increases lethality in endotoxemia. Cooperative effects of macrophage inflammatory protein-2 and tumor necrosis factor. J Immunol 1995;155:2222–2229.PubMedGoogle Scholar
  75. 75.
    Cox G: IL-10 enhances resolution of pulmonary inflammation in vivo by promoting apoptosis of neutrophils. Am J Physiol 1996; 271:L566–571.PubMedGoogle Scholar
  76. 76.
    Mulligan MS, Jones ML, Vaporciyan AA, Howard MC, Ward PA: Protective effects of IL-4 and IL-10 against immune complex-induced lung injury. J Immunol 1993;151:5666–5674.PubMedGoogle Scholar
  77. 77.
    Greenberger MJ, Strieter RM, Kunkel SL, Danforth JM, Goodman RE, Standiford TJ: Neutralization of IL-10 increases survival in a murine model ofKlebsiella pneumonia. J Immunol 1995;155:722–729.PubMedGoogle Scholar
  78. 78.
    van der Poll T, Marchant A, Keogh CV, Goldman M, Lowry SF: Interleukin-10 impairs host defense in murine pneumococcal pneumonia. J Infect Dis 1996;174:994–1000.PubMedGoogle Scholar
  79. 79.
    Vecchiarelli A, Retini C, Monari C, Tascini C, Bistoni F, Kozel TR: Purified capsular poly saccharide ofCryptococcus neoformans induces interleukin-10 secretion by human monocytes. Infect Immun 1996; 64:2846–2849.PubMedGoogle Scholar
  80. 80.
    Yang X, HayGlass KT, Brunham RC: Genetically determined differences in IL-10 and IFN-gamma responses correlate with clearance of Chlamydia trachomatis mouse pneumonitis infection. J Immunol 1996;156:4338–4344.PubMedGoogle Scholar
  81. 81.
    Bermudez LE, Champsi J: Infection withMycobacterium avium induces production of interleukin-10 (IL-10), and administration of anti-IL-10 antibody is associated with enhanced resistance to infection in mice. Infect Immun 1993; 61:3093–3097.PubMedGoogle Scholar
  82. 82.
    Steinhauser ML, Hogaboam CM, Kunkel SL, Lukacs NW, Strieter RM, Standiford TJ: Interleukin 10 is a major mediator of sepsisinduced impairment in lung antimicrobial host defense. J Immunol 1999;162:392–399.PubMedGoogle Scholar
  83. 83.
    Sawa T, Corry DB, Gropper MA, Ohara M, Kurahashi K, Wiener-Kronish JP: IL-10 improves lung injury and survival in Pseudomonas aeruginosa pneumonia. J Immunol 1997;159:2858–2866.PubMedGoogle Scholar
  84. 84.
    Huffnagle GB: Role of cytokines in T cell immunity to a pulmonaryCryptococcus neoformans infection. Biol Signals 1996;5:215–222.PubMedCrossRefGoogle Scholar
  85. 85.
    Huffnagle GB, Boyd MB, Street NE, Lipscomb MF: IL-5 is required for eosinophil recruitment, crystal deposition, and mononuclear cell recruitment during a pulmonaryCryptococcus neoformans infection in genetically susceptible mice (C57BL/6). J Immunol 1998; 160: 2393–2400.PubMedGoogle Scholar
  86. 86.
    Kanaly ST, Hines SA, Palmer GH: Cytokine modulation alters pulmonary clearance of Rhodococcus equi and development of granulomatous pneumonia. Infect Immun 1995;63:3037–3041.PubMedGoogle Scholar
  87. 87.
    Jain-Vora S, LeVine AM, Chroneos Z, Ross GF, Hull WM, Whitsett JA: Interleukin-4 enhances pulmonary clearance ofPseudomonas aeruginosa. Infect Immun 1998;66:4229–4236.PubMedGoogle Scholar
  88. 88.
    Papanicolaou DA, Wilder RL, Manolagas SC, Chrousos GP: The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med 1998;128:127–137.PubMedGoogle Scholar
  89. 89.
    Akira S, Taga T, Kishimoto T: Interleukin-6 in biology and medicine. Adv Immunol 1993;54:l-78.Google Scholar
  90. 90.
    Kopf M, Baumann H, Freer G, Freudenberg M, Lamers M, Kishimoto T, et al.: Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature 1994;368:339–342.PubMedCrossRefGoogle Scholar
  91. 91.
    Hack CE, De Groot ER, Felt-Bersma RJ, Nuijens JH, Strack Van Schijndel RJ, et al.: Increased plasma levels of interleukin-6 in sepsis [see comments]. Blood 1989; 74:1704–1710.PubMedGoogle Scholar
  92. 92.
    Bonten MJ, Froon AH, Gaillard CA, Greve JW, de Leeuw PW, Drent M, et al.: The systemic inflammatory response in the development of ventilator-associated pneumonia. Am J Respir Crit Care Med 1997; 156:1105–1113.PubMedGoogle Scholar
  93. 93.
    Lieberman D, Livnat S, Schlaeffer F, Porath A, Horowitz S, Levy R: IL-1 beta and IL-6 in community-acquired pneumonia: bacteremic pneumococcal pneumonia versusMycoplasma pneumoniae pneumonia. Infection 1997;25:90–94.PubMedCrossRefGoogle Scholar
  94. 94.
    Buck C, Bundschu J, Gallati H, Bartmann P, Pohlandt F: Inter-leukin-6: a sensitive parameter for the early diagnosis of neonatal bacterial infection. Pediatrics 1994; 93:54–58.PubMedGoogle Scholar
  95. 95.
    Kuster H, Weiss M, Willeitner AE, Detlefsen S, Jeremias I, Zbojan J, et al.: Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation [in process citation]. Lancet 1998; 352:1271–1277.PubMedCrossRefGoogle Scholar
  96. 96.
    Xing Z, Gauldie J, Cox G, Baumann H, Jordana M, Lei XF, Achong MK: IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest 1998; 101:311–320.PubMedGoogle Scholar
  97. 97.
    Dalrymple SA, Lucian LA, Slattery R, McNeil T, Aud DM, Fuchino S, et al.: Interleukin-6-deficient mice are highly susceptible to Listeria monocytogenes infection: correlation with inefficient neutrophilia. Infect Immun 1995; 63:2262–2268.PubMedGoogle Scholar
  98. 98.
    Dalrymple SA, Slattery R, Aud DM, Krishna M, Lucian LA, Murray R: Interleukin-6 is required for a protective immune response to systemic Escherichia coli infection. Infect Immun 1996;64:3231–3235.PubMedGoogle Scholar
  99. 99.
    van der Poll T, Keogh CV, Guirao X, Buurman WA, Kopf M, Lowry SF: Interleukin-6 gene-deficient mice show impaired defense against pneumococcal pneumonia. J Infect Dis 1997; 176:439–444.PubMedCrossRefGoogle Scholar
  100. 100.
    Nelson S: Role of granulocyte colony-stimulating factor in the immune response to acute bacterial infection in the nonneutropenic host: an overview. Clin Infect Dis 1994;18 Suppl 2:S197–204.PubMedGoogle Scholar
  101. 101.
    Pauksen K, Elfman L, Ulfgren AK, Venge P: Serum levels of granulocyte-colony stimulating factor (G-CSF) in bacterial and viral infections, and in atypical pneumonia. Br J Haematol 1994; 88:256–260.PubMedGoogle Scholar
  102. 102.
    Tazi A, Nioche S, Chastre J, Smiejan JM, Hance AJ: Spontaneous release of granulocyte colonystimulating factor (G-CSF) by alveolar macrophages in the course of bacterial pneumonia and sarcoidosis: endotoxin-dependent and endotoxin-independent G-CSF release by cells recovered by bronchoal veolar lavage. Am J Respir Cell Mol Biol 1991;4:140–147.PubMedGoogle Scholar
  103. 103.
    Bermudez LE, Young LS: Recombinant granulocyte-macrophage colony-stimulating factor activates human macrophages to inhibit growth or killMycobacterium avium complex. J Leukoc Biol 1990;48:67–73.PubMedGoogle Scholar
  104. 104.
    Blanchard DK, Michelini-Norris MB, Pearson CA, McMillen S, Djeu JY: Production of granulocyte -macrophage colony-stimulating factor (GM-CSF) by monocytes and large granular lymphocytes stimulated with Mycobacterium avium-M. intracellulare: activation of bactericidal activity by GM-CSF. Infectlmmun 1991;59:2396–2402.Google Scholar
  105. 105.
    Denis M: Tumor necrosis factor and granulocyte macrophage-colony stimulating factor stimulate human macrophages to restrict growth of virulent Mycobacterium avium and to kill avirulentM. avium: killing effector mechanism depends on the generation of reactive nitrogen intermediates. J Leukoc Biol 1991 ; 49:380–387.PubMedGoogle Scholar
  106. 106.
    Chen GH, Curtis JL, Mody CH, Christensen PJ, Armstrong LR, Toews GB: Effect of granulocytemacrophage colony-stimulating factor on rat alveolar macrophage anticryptococcal activity in vitro. J Immunol 1994; 152:724–734.PubMedGoogle Scholar
  107. 107.
    Levitz SM: Activation of human peripheral blood mononuclear cells by interleukin-2 and granulocytemacrophage colony-stimulating factor to inhibitCryptococcus neoformans. InfectImmun 1991;59: 3393–3397.Google Scholar
  108. 108.
    Hebert JC, O’Reilly M: Granulocyte -macrophage colony-stimulating factor (GM-CSF) enhances pulmonary defenses against pneumococcal infections after splenectomy. JTrauma 1996;41:663–666.Google Scholar
  109. 109.
    Mandujano IF, D’Souza NB, Nelson S, Summer WR, Beckerman RC, Shellito JE: Granulocyte-macrophage colony stimulating factor and Pneumocystis carinii pneumonia in mice. Am J Respir Crit Care Med 1995;151:1233–1238.PubMedGoogle Scholar
  110. 110.
    Lister PD, Gentry MJ, Preheim LC: Granulocyte colony-stimulating factor protects control rats but not ethanol-fed rats from fatal pneumococcal pneumonia. J Infect Dis 1993;168:922–926.PubMedGoogle Scholar
  111. 111.
    Preheim LC, Snitily MU, Gentry MJ: Effects of granulocyte colony-stimulating factor in cirrhotic rats with pneumococcal pneumonia. J Infect Dis 1996; 174:225–228.PubMedGoogle Scholar
  112. 112.
    Nelson S, Summer W, Bagby G, Nakamura C, Stewart L, Lipscomb G, et al.: Granulocyte colony-stimulating factor enhances pulmonary host defenses in normal and ethanol-treated rats. J Infect Dis 1991; 164:901–906.PubMedGoogle Scholar
  113. 113.
    Smith WS, Sumnicht GE, Sharpe RW, Samuelson D, Millard FE: Granulocyte colony-stimulating factor versus placebo in addition to penicillin G in a randomized blinded study of gram-negative pneumonia sepsis: analysis of survival and multisystem organ failure. Blood 1995;86:1301–1309.PubMedGoogle Scholar
  114. 114.
    Freeman BD, Quezado Z, Zeni F, Natanson C, Danner RL, Banks S, et al.: rG-CSF reduces endotoxemia and improves survival during E. coli pneumonia. J Appl Physiol 1997;83:1467–1475.PubMedGoogle Scholar
  115. 115.
    Nelson S, Belknap SM, Carlson RW, Dale D, DeBoisblanc B, Farkas S, et al.: A randomized controlled trial of filgrastim as an adjunct to antibiotics for treatment of hospitalized patients with community-acquired pneumonia. CAP Study Group. J Infect Dis 1998; 178: 1075–1080.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1999

Authors and Affiliations

  1. 1.Department of Medicine, Division of Pulmonary and Critical Care MedicineUniversity of Michigan Medical SchoolAnn Arbor
  2. 2.University of Michigan Medical CenterAnn Arbor

Personalised recommendations