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Published on: February 9, 2014
Methotrexate Ameliorates Systemic Inflammation and Septic Associated-Lung Damage in a Cecal Ligation and Puncture
Josep Bringué1,2,3, Raquel Guillamat-Prats1,2, Maria Luisa Martinez4
1Institut d' Investigació i Innovació Parc Taulí (I3PT), 08201 Sabadell, Spain.
Background:
Sepsis is a serious, heterogeneous clinical entity produced by a severe and systemic host inflammatory response to infection. Methotrexate (MTX) is a folate-antagonist that induces the generation of adenosine and also inhibits JAK/STAT pathway; MTX it is widely used as an anti-inflammatory drug to control the immune system.
Objective:
The aim of this study was to assess the beneficial effects of a single and low dose of MTX in the systemic response and acute lung injury (ALI) induced by sepsis. As in the clinics, we treated our animals with antibiotics and fluids and performed the source control to mimic the current clinic treatment.
Methods And Main Results:
Sepsis was induced in rats by a cecal ligation puncture (CLP) procedure. Six hours after induction of sepsis, we proceeded to the source control; fluids and antibiotics were administered at 6 h and 24 h after CLP. MTX (2.5 mg/Kg) was administered 6 h after the first surgery in one CLP experimental group and to one Sham group. A protective effect of MTX was observed through a significant reduction of pro-inflammatory cytokines and a decrease infiltration of inflammatory cells in the lung. In addition, we found a regulation in adenosine receptor A2aR and the metalloproteinases by MTX.
Conclusion:
A single, low dose of MTX attenuates sepsis lung-associated damage by decreasing pro-inflammatory response, infiltration of pro-inflammatory cells and avoiding defective tissue lung remodeling.
Insights
A single, low dose of methotrexate (MTX) reduces sepsis-induced systemic inflammation and acute lung injury. This treatment lowers pro-inflammatory cytokines and inflammatory cell infiltration in the lungs, offering a protective effect against sepsis complications.
Area of Science:
- Immunology
- Pharmacology
- Pulmonology
Background:
- Sepsis is a life-threatening systemic inflammatory response to infection.
- Methotrexate (MTX), a folate antagonist, is used for its anti-inflammatory properties by modulating immune responses.
- MTX influences adenosine generation and JAK/STAT signaling pathways.
Purpose of the Study:
- To evaluate the protective effects of a single, low-dose methotrexate (MTX) on sepsis-induced systemic response and acute lung injury (ALI).
- To simulate clinical sepsis treatment protocols, including antibiotics and fluid resuscitation, alongside MTX administration.
Main Methods:
- Sepsis was induced in rats using the cecal ligation and puncture (CLP) model.
- Animals received antibiotics and fluids starting 6 hours post-CLP.
- A single dose of MTX (2.5 mg/Kg) was administered 6 hours after CLP.
Main Results:
- MTX treatment significantly reduced pro-inflammatory cytokines and inflammatory cell infiltration in the lungs.
- A protective effect against sepsis-induced acute lung injury was observed.
- MTX modulated adenosine receptor A2aR and metalloproteinase expression.
Conclusions:
- A single, low dose of MTX attenuates sepsis-associated lung damage.
- MTX decreases the pro-inflammatory response and inflammatory cell infiltration in sepsis.
- MTX treatment helps prevent defective lung tissue remodeling during sepsis.
