The Mechanisms and Significances of Synergistic Effects of Mycophenolic Acid and LPS on IL-1β Secretion by Mononuclear

Lupus Nephritis Clinical Trial

Official title:

The Mechanisms and Significances of Synergistic Effects of Mycophenolic Acid and Lipopolysaccharide on Interleukin-1β Secretion by Mononuclear

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02435368
• Other study ID #: 201501001
• Status: Recruiting
• Phase: N/A
• First received: April 25, 2015
• Last updated: April 30, 2015
• Start date: April 2015
• Est. completion date: March 2016

Study information

• Verified date: April 2015
• Source: The Third Affiliated Hospital of Southern Medical University
• Contact: erwei Sun, doctor
• Phone: +86 020-62784421
• Email: ewsun[@]263.net
• Is FDA regulated: No
• Health authority: China: Health and Family Planning Commission of Guangdong Province
• Study type: Observational

Clinical Trial Summary

To determine the mechanisms and significances of synergistic effects of mycophenolic acid and LPS on IL-1β secretion by mononuclear

Description:

Mycophenolate mofetil (MMF), which inhibits T and B lymphocyte proliferation, is widely used to treat a variety of autoimmune diseases, such as systemic lupus erythematosus (SLE) and lupus nephritis (LN). We are the first to show that mycophenolic acid (MPA), the active metabolite of MMF, in association with lipopolysaccharide (LPS), is able to promote the secretion of interleukin (IL)-1β, which contradicts the traditional conception that immunosuppressants inhibit the secretion of inflammatory factors.

In this study, we first determined the effects of MPA in association with LPS on IL-1β production. Then, we explored whether the synergized effect on IL-1β production was mediated through the nuclear factor （NF）-κB pathway that produces more pro-IL-1β, or through the triggering of NLRP3 inflammasome that leads to enhanced activation of caspase-1 and accelerated degradation of pro-IL-1β into mature IL-1β.

This study is not only conducive to clarify the mechanisms, signal transduction pathways and potential clinical significances of IL-1β production in LPS and MPA combined treatment, but also to provide experimental data as well as theoretical rationales for more effective and more logical immunosuppressive protocols.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: March 2016
• Est. primary completion date: November 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Healthy Volunteers,age 18-60.

Exclusion Criteria:

• Don't agree with informed consent

Study Design

Observational Model: Case-Only, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Lupus Nephritis

Intervention

Drug:
• mycophenolic acid
Monocytes were co-cultured with LPS and/or MPA.After 12 hours, the supernatants were harvested and stored at -80°C for ELISA.

Locations

Country	Name	City	State
China	Third Affiliated Hospital of Southern Medical University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
The Third Affiliated Hospital of Southern Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	mean ± SD of percentage of IL-1ß production induced by Lipopolysaccharide in associate with MPA in monocytes.		six months	No