Fusidic acid, an immunosuppressive drug with functions similar to cyclosporin A

doi:10.1016/1043-4666(90)90051-T

Cytokine

Volume 2, Issue 6, November 1990, Pages 423-429

https://doi.org/10.1016/1043-4666(90)90051-T Get rights and content

Abstract

Fusidic acid, a tetracyclic triterpenoic acid, is used for local and systemic treatment of bacterial infections. Its in vitro effects on the human immune response were tested. Activated blood mononuclear cells released lower levels of interleukin (IL) 1 in the presence of nontoxic and clinically attainable levels of fusidic acid (15 to 50 μg/mL). In contrast, the drug failed to affect the production of two other monocyte-derived cytokines, tumor necrosis factor (TNF)-α and IL 6. The production of the T-cell—derived cytokines, IL 2 and interferon-γ (IFN-γ), were also suppressed (IC₅₀: 5 to 15 μg/mL). The early costimulatory effects of IL 1 and IL 6 on mouse thymocytes and human T cells were suppressed by similar levels of the drug, as was the hybridoma growth-promoting function of IL 6. T-cell proliferation induced by phytohemagglutinin or allogeneic cells was reversibly inhibited (IC₅₀: 15 μg/mL). These functions of fusidic acid were strikingly similar to those of cyclosporin A. Because of the low toxicity of the former, it may have a role as a clinically useful suppressor of immunoinflammatory processes.

References (27)

K Bendtzen
Interleukin 1, interleukin 6 and tumor necrosis factor in infection, inflammation and immunity
Immunol Lett
(1988)
W von Daehne et al.
Structure-activity relationships in fusidic acid-type antibiotics
Adv Appl Microbiol
(1979)
JS Goodwin et al.
Regulation of the immune response by prostaglandins
Clin Immunol Immunopathol
(1980)
K Bendtzen
Immune hormones (cytokines); pathogenic role in autoimmune rheumatic diseases and endocrine diseases
Autoimmunity
(1989)
PE Auron et al.
Nucleotide sequence of human monocyte interleukin 1 precursor cDNA
CJ March et al.
Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs
Nature
(1985)
S Gillis et al.
T cell growth factor: parameters of production and a quantitative microassay for activity
J Immunol
(1978)
SB Mizel
Interleukin 1 and T cell activation
Immunol Rev
(1982)
W Falk et al.
IL-1 induces high affinity IL-2 receptor expression of CD4-8-thymocytes
J Immunol
(1989)
LA Aarden et al.
Production of hybridoma growth factor by human monocytes
Eur J Immunol
(1987)

T Kishimoto et al.

Molecular regulation of B lymphocyte response

Annu Rev Immunol

(1988)

K Yamasaki et al.

Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor

Science

(1988)

WO Godtfredsen et al.

Fusidic acid: a new antibiotic

Nature

(1962)

Cited by (45)

Research, development and pharmacological activity of fusidic acid and its derivatives
2023, Journal of Molecular Structure
Fusidic acid is a tetracyclic triterpenoid isolated from fungi. Fusidic acid has a wide range of pharmacological activities, including anti-inflammatory, antimalarial, antiparasitic and antiviral activities. Among them, in the field of antibacterial shows a strong efficacy. The latest research progress on the pharmacological effects and structural modification of fusidic acid was reviewed by integrating and analyzing external related literature. Future research on fusidic acid will focus on improving the efficacy, opening up new pharmacological activities and structural modifications. We hope this review provides useful information for drug discovery of fusidic acid derivatives.
Biodegradation of environmental pollutant through pathways engineering and genetically modified organisms approaches
2020, Microorganisms for Sustainable Environment and Health
Genetically modified organism (GMO) is a term used frequently for the organism whose genetic makeup has been modified using recombinant DNA technology (r-DNA technology). In the modern era GMOs are used in medical and biological applications, gene therapy (knockout mouse), production of pharmaceutical products (Insulin), agriculture (Golden rice), Bt crop (Bt Cotton), and environmental safety like bioremediation. The use of genetic engineering approaches has altered several metabolic pathways in microorganism and plants that have been improved for the degradation and bioaccumulation of hazardous environmental pollutants, a process known as bioremediation. Here in this book chapter we are focusing on the possibilities of genetic engineering/pathway engineering approaches for the removal of environmental waste using GMO approaches. In phytoremediation genetically improved/designed plants are used for the removal of toxic heavy metals. These processes are environment-friendly. In mycoremediation, mycorrhizal fungi are involved in the degradation of toxic and harmful pollutants. Despite the fact that the horizontal type of gene transfer is common in nature, unknown effects can be possible by making alterations in the natural state of an organism by expressing a foreign gene. Such modifications can affect the growth rate, metabolism, and/or response to environmental factors of the organism. There are some issues with GMO like their long-term effects, gene stability, and their effect on other organisms, including with respect to human and environmental safety. However, there are no definite ways to ensure that such unexpected consequences will not occur.
Suppression of experimental autoimmune myocarditis by sodium fusidate (fusidin)
2005, Pharmacological Research
Fusidic acid and its sodium salt sodium fusidate (fusidin) are widely used antibiotics that possess immunomodulating properties. It has been shown that fusidin ameliorates the course of several organ-specific immunoinflammatory diseases and thus we investigated the effect of fusidin on myosin-induced experimental autoimmune myocarditis (EAM) in rats, a well-established animal model for human giant cell myocarditis and postmyocarditis dilated cardiomyopathy (DCM).
Fusidin at doses of 80 mg kg⁻¹ was administrated i.m. to male Dark Agouti (DA) rats, either from days 0 to 10 (early treatment group), or from days 10 to 20 (late treatment group) after induction of EAM. Efficacy of fusidin treatment was determined on day 21 of EAM development. It was observed that both early and late treatment with fusidin markedly ameliorated clinical, histological and immunohistochemical signs of the disease. The treated rats had significantly decreased incidence of EAM, heart weight and heart weight/body weight ratio (Hw/Bw) compared with untreated animals. In contrast to the severe myocardial damage and cellular infiltration in the EAM rats, there was only focal infiltration of inflammatory cells in the myocardium of the treated rats. In both treated groups the mean microscopic score was markedly lower compared with vehicle-treated animals. In addition, the number of CD4+, ED1+ and OX6+ cells was significantly lower in myocardium of fusidin-treated rats than that in untreated group. The present findings suggest that fusidin exhibited both early and late therapeutical effect in EAM.
Curative effects of sodium fusidate on the development of dinitrobenzenesulfonic acid-induced colitis in rats
2003, Clinical Immunology
Fusidic acid and sodium fusidate (fusidin) are antibiotics with low toxicity and powerful immunomodulatory activities in vitro and in vivo. In this study we have evaluated the effect of fusidin on the development of dinitrobenzenesulfonic acid (DNB)-induced colitis in rats that serves as a preclinical model of human inflammatory bowel disease (IBD). The data show that when administered orally at the dose of 80 (but not 40) mg/kg body wt under a “therapeutic” regimen soon after DNB application, fusidin significantly ameliorates clinical, histological, and seroimmunological signs of disease. These entailed a significant reduction in body weight loss, smaller increase in colon weights, milder macroscopic damage, and lower histological scores. In addition, when sacrificed at the end of the study, fusidin-treated rats had significantly lower blood levels of tumor necrosis factor α and interferon-γ compared with untreated controls. The present findings concur with the beneficial actions of fusidin in a pilot study conducted in patients with Crohn's disease and warrant controlled studies in humans with IBD.
Sodium fusidate ameliorates the course of diabetes induced in mice by multiple low doses of streptozotocin
2000, Journal of Autoimmunity
We studied the effects of the immunosuppressant sodium fusidate (fusidin) on murine immunoinflammatory diabetes mellitus (DM) induced by multiple low doses of streptozotocin (SZ). Fusidin was given by gavage to three strains of mice (C57KsJ, C57BL/6, CD1) at doses 10 or 100 mg/kg body weight every other day. The drug was administered as an early or late prophylactic regime starting either 1 day prior to the first or after the fifth and last injection of SZ. In both situations the largest dose of fusidin successfully reduced the clinical, chemical and histological signs of DM, the treated mice having significantly lower glycaemic values and milder (often absent) insulitis compared with sham-treated animals or controls given SZ alone. The antidiabetogenic effect was long-lasting as it was maintained up to 1 month after cessation of therapy. In contrast, fusidin prophylaxis failed to prevent development of hyperglycaemia acutely induced by one single and high (160 mg/kg) dose of SZ, which is a model of DM primarily due to the toxic action of SZ on the β cells and does not involve immunopathogenetic mechanisms.
On day 14 after SZ, fusidin markedly altered the circulating cytokine profile inducedin vivo by ConA, reducing the levels of IFN-γ, IL-2 and TNF-α and augmenting the level of IL-6. However, only the inhibitory effect of the drug on the synthesis/release of IFN-γ seemed to be causally related to its capacity to counteract the SZ-induced DM. In fact, the disease was prevented by a neutralizing monoclonal antibody (mAb) against IFN-γ, but not by anti-IL-2 receptor mAb, a soluble form of TNF-receptor type 1 or recombinant human IL-6. The prevention of disease by fusidin was also partly reversed by exogenously administered recombinant mouse IFN-γ.
The data provide furtherin-vivo evidence for the anti-diabetogenic and immunomodulatory properties of fusidin and indicate that this drug could have a role in prevention and treatment of human type 1 DM.
Amelioration of experimental allergic neuritis by sodium fusidate (fusidin): Suppression of IFN-γ and TNF-α and enhancement of IL-10
1999, Journal of Autoimmunity
The immunomodulating antibiotic drug fusidic acid and its sodium salt sodium fusidate (fusidin) ameliorate several organ-specific immunoinflammatory diseases. Because preliminary observations suggest that fusidin may also exert a beneficial effect in Guillain-Barré syndrome (GBS), here we have studied the effects of fusidin on actively induced experimental autoimmune neuritis (EAN) in rats, a known animal model for GBS. Both prophylactic and therapeutic treatment with fusidin (4 mg/rat day ip) markedly ameliorated the clinical course of the disease compared to vehicle-treated animals. The beneficial effects were associated with profound modifications of the capacity of these rats to produce and release pro- and anti-inflammatory cytokines such as IFN-γ, TNF-α and IL-10, which are important in regulating the development of EAN.

View all citing articles on Scopus

View full text

Original contributionFusidic acid, an immunosuppressive drug with functions similar to cyclosporin A

Abstract

Immunol Lett

Adv Appl Microbiol

Clin Immunol Immunopathol

Immune hormones (cytokines); pathogenic role in autoimmune rheumatic diseases and endocrine diseases

Autoimmunity

Nucleotide sequence of human monocyte interleukin 1 precursor cDNA

Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs

Nature

T cell growth factor: parameters of production and a quantitative microassay for activity

J Immunol

Interleukin 1 and T cell activation

Immunol Rev

IL-1 induces high affinity IL-2 receptor expression of CD4-8-thymocytes

J Immunol

Production of hybridoma growth factor by human monocytes

Eur J Immunol

Molecular regulation of B lymphocyte response

Annu Rev Immunol

Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor

Science

Fusidic acid: a new antibiotic

Nature

Original contribution
Fusidic acid, an immunosuppressive drug with functions similar to cyclosporin A