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. 1995 Jun;115(4):684–688. doi: 10.1111/j.1476-5381.1995.tb14987.x

Cytokine-mediated inflammatory hyperalgesia limited by interleukin-10.

S Poole 1, F Q Cunha 1, S Selkirk 1, B B Lorenzetti 1, S H Ferreira 1
PMCID: PMC1908480  PMID: 7582491

Abstract

1. The effect of interleukin-10 (IL-10) upon the hyperalgesic activities in rats of bradykinin, tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), prostaglandin E2 (PGE2) and carrageenin were investigated in a model of mechanical hyperalgesia. 2. Hyperalgesic responses to bradykinin (1 micrograms) were inhibited in a dose-dependent manner by prior treatment with IL-10 (1-100 ng). 3. Hyperalgesic responses to TNF alpha (2.5 pg), IL-1 beta (0.5 pg) and IL-6 (1.0 ng) but not to IL-8 (0.1 ng) and PGE2 (50 ng and 100 ng) were inhibited by prior treatment with IL-10 (10 ng). 4. Hyperalgesic responses to carrageenin (100 micrograms) were inhibited by IL-10 (10 ng) when this cytokine was injected before but not after the carrageenin. 5. A monoclonal antibody to mouse IL-10 potentiated the hyperalgesic responses to carrageenin (10 micrograms) and TNF alpha (0.025 pg) but not that to IL-8 (0.01 ng). 6. In in vitro experiments in human peripheral blood mononuclear cells (MNCs), IL-10 (0.25-4.0 ng ml-1) inhibited in a dose-dependent manner PGE2 production by MNCs stimulated with IL-1 beta (1-64 ng ml-1) or endotoxin (lipopolysaccharide, LPS, 1 iu = 143 pg ml-1) but evoked only small increases in IL-1ra production. 7. These data suggest that IL-10 limits the inflammatory hyperalgesia evoked by carrageenin and bradykinin by two mechanisms: inhibition of cytokine production and inhibition of IL-1 beta evoked PGE2 production.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Angel J., Berenbaum F., Le Denmat C., Nevalainen T., Masliah J., Fournier C. Interleukin-1-induced prostaglandin E2 biosynthesis in human synovial cells involves the activation of cytosolic phospholipase A2 and cyclooxygenase-2. Eur J Biochem. 1994 Nov 15;226(1):125–131. doi: 10.1111/j.1432-1033.1994.tb20033.x. [DOI] [PubMed] [Google Scholar]
  2. Bogdan C., Vodovotz Y., Nathan C. Macrophage deactivation by interleukin 10. J Exp Med. 1991 Dec 1;174(6):1549–1555. doi: 10.1084/jem.174.6.1549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cunha F. Q., Lorenzetti B. B., Poole S., Ferreira S. H. Interleukin-8 as a mediator of sympathetic pain. Br J Pharmacol. 1991 Nov;104(3):765–767. doi: 10.1111/j.1476-5381.1991.tb12502.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cunha F. Q., Poole S., Lorenzetti B. B., Ferreira S. H. The pivotal role of tumour necrosis factor alpha in the development of inflammatory hyperalgesia. Br J Pharmacol. 1992 Nov;107(3):660–664. doi: 10.1111/j.1476-5381.1992.tb14503.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ferreira S. H., Lorenzetti B. B., Bristow A. F., Poole S. Interleukin-1 beta as a potent hyperalgesic agent antagonized by a tripeptide analogue. Nature. 1988 Aug 25;334(6184):698–700. doi: 10.1038/334698a0. [DOI] [PubMed] [Google Scholar]
  6. Ferreira S. H., Lorenzetti B. B., Corrêa F. M. Central and peripheral antialgesic action of aspirin-like drugs. Eur J Pharmacol. 1978 Dec 15;53(1):39–48. doi: 10.1016/0014-2999(78)90265-0. [DOI] [PubMed] [Google Scholar]
  7. Ferreira S. H., Lorenzetti B. B., Poole S. Bradykinin initiates cytokine-mediated inflammatory hyperalgesia. Br J Pharmacol. 1993 Nov;110(3):1227–1231. doi: 10.1111/j.1476-5381.1993.tb13946.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ferreira S. H. Prostaglandins, aspirin-like drugs and analgesia. Nat New Biol. 1972 Dec 13;240(102):200–203. doi: 10.1038/newbio240200a0. [DOI] [PubMed] [Google Scholar]
  9. Fiorentino D. F., Bond M. W., Mosmann T. R. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989 Dec 1;170(6):2081–2095. doi: 10.1084/jem.170.6.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fiorentino D. F., Zlotnik A., Mosmann T. R., Howard M., O'Garra A. IL-10 inhibits cytokine production by activated macrophages. J Immunol. 1991 Dec 1;147(11):3815–3822. [PubMed] [Google Scholar]
  11. Howard M., O'Garra A. Biological properties of interleukin 10. Immunol Today. 1992 Jun;13(6):198–200. doi: 10.1016/0167-5699(92)90153-X. [DOI] [PubMed] [Google Scholar]
  12. Howard M., O'Garra A., Ishida H., de Waal Malefyt R., de Vries J. Biological properties of interleukin 10. J Clin Immunol. 1992 Jul;12(4):239–247. doi: 10.1007/BF00918147. [DOI] [PubMed] [Google Scholar]
  13. Jenkins J. K., Malyak M., Arend W. P. The effects of interleukin-10 on interleukin-1 receptor antagonist and interleukin-1 beta production in human monocytes and neutrophils. Lymphokine Cytokine Res. 1994 Feb;13(1):47–54. [PubMed] [Google Scholar]
  14. Mertz P. M., DeWitt D. L., Stetler-Stevenson W. G., Wahl L. M. Interleukin 10 suppression of monocyte prostaglandin H synthase-2. Mechanism of inhibition of prostaglandin-dependent matrix metalloproteinase production. J Biol Chem. 1994 Aug 19;269(33):21322–21329. [PubMed] [Google Scholar]
  15. Nakamura M., Ferreira S. H. A peripheral sympathetic component in inflammatory hyperalgesia. Eur J Pharmacol. 1987 Mar 17;135(2):145–153. doi: 10.1016/0014-2999(87)90606-6. [DOI] [PubMed] [Google Scholar]
  16. Oswald I. P., Wynn T. A., Sher A., James S. L. 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 U S A. 1992 Sep 15;89(18):8676–8680. doi: 10.1073/pnas.89.18.8676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Poole S., Bristow A. F., Selkirk S., Rafferty B. Development and application of radioimmunoassays for interleukin-1 alpha and interleukin-1 beta. J Immunol Methods. 1989 Jan 17;116(2):259–264. doi: 10.1016/0022-1759(89)90212-3. [DOI] [PubMed] [Google Scholar]
  18. Ralph P., Nakoinz I., Sampson-Johannes A., Fong S., Lowe D., Min H. Y., Lin L. IL-10, T lymphocyte inhibitor of human blood cell production of IL-1 and tumor necrosis factor. J Immunol. 1992 Feb 1;148(3):808–814. [PubMed] [Google Scholar]
  19. Taktak Y. S., Selkirk S., Bristow A. F., Carpenter A., Ball C., Rafferty B., Poole S. Assay of pyrogens by interleukin-6 release from monocytic cell lines. J Pharm Pharmacol. 1991 Aug;43(8):578–582. doi: 10.1111/j.2042-7158.1991.tb03540.x. [DOI] [PubMed] [Google Scholar]
  20. Zlotnik A., Moore K. W. Interleukin 10. Cytokine. 1991 Sep;3(5):366–371. doi: 10.1016/1043-4666(91)90039-g. [DOI] [PubMed] [Google Scholar]
  21. de Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., de Vries J. E. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209–1220. doi: 10.1084/jem.174.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. de Waal Malefyt R., Haanen J., Spits H., Roncarolo M. G., te Velde A., Figdor C., Johnson K., Kastelein R., Yssel H., de Vries J. E. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med. 1991 Oct 1;174(4):915–924. doi: 10.1084/jem.174.4.915. [DOI] [PMC free article] [PubMed] [Google Scholar]

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