| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Immunology, Vol 151, Issue 7 3682-3692, Copyright © 1993 by American Association of Immunologists
ARTICLES |
DE Hatzigeorgiou, S He, J Sobel, KH Grabstein, A Hafner and JL Ho
Department of Medicine, Cornell University Medical College, New York, NY 10021.
IL-6 is a cytokine synthesized by T cells and macrophages (M phi). It has pleiotropic effects on diverse cell types and is recognized for its "pro-inflammatory" properties. In mice, IL-4, IL-5, IL-6, and IL-10 are produced by Th-2 cells. Because IL-10 suppresses Th-1 clones, and IL-4 broadly deactivates M phi, experiments were carried out to investigate the in vitro effects of recombinant human IL-6 on cytokine activation of human M phi. Pretreatment with IL-6 induced a dose- and time- dependent suppression of IFN-gamma (1000 U/mL) and TNF-alpha (25 ng/mL) activation of M phi for the killing of L. amazonensis. At doses greater than 0.1 to 100 ng/mL, IL-6 inhibited IFN-gamma and TNF-alpha activation by 21 to 93% and 36 to 82%, respectively. IL-6 alone had no effect on M phi viability and intracellular L. amazonensis growth. Blockade of M phi activation was greatest when IL-6 was added 24 or 48 h before infection and treatment with IFN-gamma or TNF-alpha. Furthermore, mAb against IL-6 abrogated the inhibitory activity of IL- 6. Similarly IL-6 pretreatment suppressed M phi activation for antileishmanial capacity by IL-3, granulocyte-monocyte-CSF (GM-CSF) and IL-1 beta. Because cytokine induction of antileishmanial activity is associated with enhancement of oxidative capacity, the effect of IL-6 on this mechanism was evaluated. Pretreatment with IL-6 down-modulated TNF-alpha (25 ng/mL) enhancement of M phi oxidative capacity in a dose- and time-dependent manner. A similar depression of oxidative capacity was observed for GM-CSF and IL-3 but not for IFN-gamma. Furthermore, NG- monomethyl-L-arginine (a nitric oxide synthase inhibitor) had no effect on IFN-gamma and TNF-alpha activation of antileishmanial activity and nitrites/nitrates were not reliably assayed from M phi culture supernatants. These findings suggest that IL-6 down-modulates cytokine activation of M phi antileishmanial capacity by inhibiting oxygen- dependent and undefined oxygen-independent mechanisms.
This article has been cited by other articles:
|
|
 |
|
  H. W. Murray Accelerated Control of Visceral Leishmania donovani Infection in Interleukin-6-Deficient Mice Infect. Immun., September 1, 2008; 76(9): 4088 - 4091. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. H. Wheat, K. E. Pauken, R. V. Morris, and R. G. Titus Lutzomyia longipalpis Salivary Peptide Maxadilan Alters Murine Dendritic Cell Expression of CD80/86, CCR7, and Cytokine Secretion and Reprograms Dendritic Cell-Mediated Cytokine Release from Cultures Containing Allogeneic T Cells J. Immunol., June 15, 2008; 180(12): 8286 - 8298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Brodie, M. C. Smith, R. V. Morris, and R. G. Titus Immunomodulatory Effects of the Lutzomyia longipalpis Salivary Gland Protein Maxadilan on Mouse Macrophages Infect. Immun., May 1, 2007; 75(5): 2359 - 2365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Vasquez and L. Soong CXCL10/Gamma Interferon-Inducible Protein 10-Mediated Protection against Leishmania amazonensis Infection in Mice Infect. Immun., December 1, 2006; 74(12): 6769 - 6777. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Costa, C. Favali, J. Clarencio, L. Afonso, V. Conceicao, J. C. Miranda, R. G. Titus, J. Valenzuela, M. Barral-Netto, A. Barral, et al. Lutzomyia longipalpis Salivary Gland Homogenate Impairs Cytokine Production and Costimulatory Molecule Expression on Human Monocytes and Dendritic Cells Infect. Immun., March 1, 2004; 72(3): 1298 - 1305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Anstead, B. Chandrasekar, Q. Zhang, and P. C. Melby Multinutrient undernutrition dysregulates the resident macrophage proinflammatory cytokine network, nuclear factor-{kappa}B activation, and nitric oxide production J. Leukoc. Biol., December 1, 2003; 74(6): 982 - 991. [Abstract] [Full Text]
|
|
|
|
|
|
M. Rodriguez-Sosa, L. E. Rosas, J. R. David, R. Bojalil, A. R. Satoskar, and L. I. Terrazas Macrophage Migration Inhibitory Factor Plays a Critical Role in Mediating Protection against the Helminth Parasite Taenia crassiceps Infect. Immun., March 1, 2003; 71(3): 1247 - 1254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Delorenzi, L. Freire-de-Lima, C. R. Gattass, D. de Andrade Costa, L. He, M. E. Kuehne, and E. M. B. Saraiva In Vitro Activities of Iboga Alkaloid Congeners Coronaridine and 18-Methoxycoronaridine against Leishmania amazonensis Antimicrob. Agents Chemother., July 1, 2002; 46(7): 2111 - 2115. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. K. F. de Miranda Santos, C. H. N. Costa, H. Krieger, M. F. Feitosa, D. Zurakowski, B. Fardin, R. B. B. Gomes, D. L. Weiner, D. A. Harn, R. A. B. Ezekowitz, et al. Mannan-Binding Lectin Enhances Susceptibility to Visceral Leishmaniasis Infect. Immun., August 1, 2001; 69(8): 5212 - 5215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Satoskar, M. Bozza, M. Rodriguez Sosa, G. Lin, and J. R. David Migration-Inhibitory Factor Gene-Deficient Mice Are Susceptible to Cutaneous Leishmania major Infection Infect. Immun., February 1, 2001; 69(2): 906 - 911. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Alexander, A. Satoskar, and D. Russell Leishmania species: models of intracellular parasitism J. Cell Sci., January 9, 1999; 112(18): 2993 - 3002. [Abstract] [PDF]
|
|
|
|
 |
|
 D. E. Hatzigeorgiou, J. Geng, B. Zhu, Y. Zhang, K. Liu, W. N. Rom, M. J. Fenton, S. J. Turco, and J. L. Ho Lipophosphoglycan from Leishmania suppresses agonist-induced interleukin 1beta gene expression in human monocytes via a unique promoter sequence PNAS, December 10, 1996; 93(25): 14708 - 14713. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
