Minocycline in the treatment of patients with primary sclerosing cholangitis

Results of a pilot study

Marina G. Silveira, Natalie J. Torok, Andrea A. Gossard, Jill C. Keach, Roberta A. Jorgensenrn, Janice L. Petzrn, Keith Lindor

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

OBJECTIVES: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of young adults that is associated with significant morbidity and mortality. No effective medical therapy is available. Minocycline has been found to exert biological effects independent of its antimicrobial properties, including anti-inflammatory activities such as inhibition of inducible nitric oxide synthase, upregulation of interleukin 10, and direct suppressive effect on B- and T-cell function. Minocycline may also inhibit cell death pathways by reducing both proapoptotic and proinflammatory enzyme activation. We sought to investigate the safety and efficacy of minocycline among patients with PSC. METHODS: We evaluated the efficacy of minocycline in patients with PSC in a pilot study. Sixteen patients with PSC were enrolled. Minocycline, 100mg orally twice daily, was given for 1 year. RESULTS: A statistically significant improvement in serum alkaline phosphatase activity (330Ul vs. 265Ul, P0.04) and Mayo risk score (0.55 vs. 0.02, P0.05) occurred with treatment. Serum bilirubin and albumin remained essentially unchanged while on treatment. CONCLUSIONS: The results of this pilot study indicate that minocycline is reasonably well tolerated and potentially effective in patients with PSC. These findings might be explained by the anti-inflammatory and antiapoptotic properties of minocycline. Though the data presented are too preliminary to support the clinical use of minocycline in the treatment of PSC at this time, its use should be further investigated.

Original languageEnglish (US)
Pages (from-to)83-88
Number of pages6
JournalAmerican Journal of Gastroenterology
Volume104
Issue number1
DOIs
StatePublished - Jan 2009
Externally publishedYes

Fingerprint

Sclerosing Cholangitis
Minocycline
Therapeutics
Anti-Inflammatory Agents
Enzyme Activation
Nitric Oxide Synthase Type II
Bilirubin
Serum Albumin
Interleukin-10
Alkaline Phosphatase
Liver Diseases
Young Adult
Cell Death
Up-Regulation
Morbidity
T-Lymphocytes
Safety
Mortality

ASJC Scopus subject areas

  • Gastroenterology
  • Medicine(all)

Cite this

Minocycline in the treatment of patients with primary sclerosing cholangitis : Results of a pilot study. / Silveira, Marina G.; Torok, Natalie J.; Gossard, Andrea A.; Keach, Jill C.; Jorgensenrn, Roberta A.; Petzrn, Janice L.; Lindor, Keith.

In: American Journal of Gastroenterology, Vol. 104, No. 1, 01.2009, p. 83-88.

Research output: Contribution to journalArticle

Silveira, Marina G. ; Torok, Natalie J. ; Gossard, Andrea A. ; Keach, Jill C. ; Jorgensenrn, Roberta A. ; Petzrn, Janice L. ; Lindor, Keith. / Minocycline in the treatment of patients with primary sclerosing cholangitis : Results of a pilot study. In: American Journal of Gastroenterology. 2009 ; Vol. 104, No. 1. pp. 83-88.
@article{79ec677bc3ce442cabae15c3b641076f,
title = "Minocycline in the treatment of patients with primary sclerosing cholangitis: Results of a pilot study",
abstract = "OBJECTIVES: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of young adults that is associated with significant morbidity and mortality. No effective medical therapy is available. Minocycline has been found to exert biological effects independent of its antimicrobial properties, including anti-inflammatory activities such as inhibition of inducible nitric oxide synthase, upregulation of interleukin 10, and direct suppressive effect on B- and T-cell function. Minocycline may also inhibit cell death pathways by reducing both proapoptotic and proinflammatory enzyme activation. We sought to investigate the safety and efficacy of minocycline among patients with PSC. METHODS: We evaluated the efficacy of minocycline in patients with PSC in a pilot study. Sixteen patients with PSC were enrolled. Minocycline, 100mg orally twice daily, was given for 1 year. RESULTS: A statistically significant improvement in serum alkaline phosphatase activity (330Ul vs. 265Ul, P0.04) and Mayo risk score (0.55 vs. 0.02, P0.05) occurred with treatment. Serum bilirubin and albumin remained essentially unchanged while on treatment. CONCLUSIONS: The results of this pilot study indicate that minocycline is reasonably well tolerated and potentially effective in patients with PSC. These findings might be explained by the anti-inflammatory and antiapoptotic properties of minocycline. Though the data presented are too preliminary to support the clinical use of minocycline in the treatment of PSC at this time, its use should be further investigated.",
author = "Silveira, {Marina G.} and Torok, {Natalie J.} and Gossard, {Andrea A.} and Keach, {Jill C.} and Jorgensenrn, {Roberta A.} and Petzrn, {Janice L.} and Keith Lindor",
year = "2009",
month = "1",
doi = "10.1038/ajg.2008.14",
language = "English (US)",
volume = "104",
pages = "83--88",
journal = "American Journal of Gastroenterology",
issn = "0002-9270",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Minocycline in the treatment of patients with primary sclerosing cholangitis

T2 - Results of a pilot study

AU - Silveira, Marina G.

AU - Torok, Natalie J.

AU - Gossard, Andrea A.

AU - Keach, Jill C.

AU - Jorgensenrn, Roberta A.

AU - Petzrn, Janice L.

AU - Lindor, Keith

PY - 2009/1

Y1 - 2009/1

N2 - OBJECTIVES: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of young adults that is associated with significant morbidity and mortality. No effective medical therapy is available. Minocycline has been found to exert biological effects independent of its antimicrobial properties, including anti-inflammatory activities such as inhibition of inducible nitric oxide synthase, upregulation of interleukin 10, and direct suppressive effect on B- and T-cell function. Minocycline may also inhibit cell death pathways by reducing both proapoptotic and proinflammatory enzyme activation. We sought to investigate the safety and efficacy of minocycline among patients with PSC. METHODS: We evaluated the efficacy of minocycline in patients with PSC in a pilot study. Sixteen patients with PSC were enrolled. Minocycline, 100mg orally twice daily, was given for 1 year. RESULTS: A statistically significant improvement in serum alkaline phosphatase activity (330Ul vs. 265Ul, P0.04) and Mayo risk score (0.55 vs. 0.02, P0.05) occurred with treatment. Serum bilirubin and albumin remained essentially unchanged while on treatment. CONCLUSIONS: The results of this pilot study indicate that minocycline is reasonably well tolerated and potentially effective in patients with PSC. These findings might be explained by the anti-inflammatory and antiapoptotic properties of minocycline. Though the data presented are too preliminary to support the clinical use of minocycline in the treatment of PSC at this time, its use should be further investigated.

AB - OBJECTIVES: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of young adults that is associated with significant morbidity and mortality. No effective medical therapy is available. Minocycline has been found to exert biological effects independent of its antimicrobial properties, including anti-inflammatory activities such as inhibition of inducible nitric oxide synthase, upregulation of interleukin 10, and direct suppressive effect on B- and T-cell function. Minocycline may also inhibit cell death pathways by reducing both proapoptotic and proinflammatory enzyme activation. We sought to investigate the safety and efficacy of minocycline among patients with PSC. METHODS: We evaluated the efficacy of minocycline in patients with PSC in a pilot study. Sixteen patients with PSC were enrolled. Minocycline, 100mg orally twice daily, was given for 1 year. RESULTS: A statistically significant improvement in serum alkaline phosphatase activity (330Ul vs. 265Ul, P0.04) and Mayo risk score (0.55 vs. 0.02, P0.05) occurred with treatment. Serum bilirubin and albumin remained essentially unchanged while on treatment. CONCLUSIONS: The results of this pilot study indicate that minocycline is reasonably well tolerated and potentially effective in patients with PSC. These findings might be explained by the anti-inflammatory and antiapoptotic properties of minocycline. Though the data presented are too preliminary to support the clinical use of minocycline in the treatment of PSC at this time, its use should be further investigated.

UR - http://www.scopus.com/inward/record.url?scp=60749089231&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=60749089231&partnerID=8YFLogxK

U2 - 10.1038/ajg.2008.14

DO - 10.1038/ajg.2008.14

M3 - Article

VL - 104

SP - 83

EP - 88

JO - American Journal of Gastroenterology

JF - American Journal of Gastroenterology

SN - 0002-9270

IS - 1

ER -