Disruption of the CD40-CD40 ligand system prevents an oxygen-induced respiratory distress syndrome.

Abstract	Oxygen therapy is a mainstay treatment for infants and adults with poor lung function. Unfortunately, oxygen itself is toxic and incites respiratory cell damage and inflammation. Therapies for oxygen-induced lung damage are nonexistent. Employing a mouse model of hyperoxic lung injury, a monoclonal anti-CD40 ligand (L) antibody (MR1), which disrupts CD40-CD40L interactions, was tested for the ability to reduce pulmonary injury. Intraperitoneal administration of MR1, either before or after oxygen exposure, was remarkably effective in reducing and in many cases preventing lung injury. The pro-inflammatory enzyme cyclooxygenase-2 (Cox-2), responsible for prostaglandin production, is massively up-regulated in the lungs after hyperoxic exposure. Immunohistochemical staining for Cox-2 revealed that MR1 greatly reduces the oxygen-induced induction of Cox-2. The remarkable effectiveness of MR1 in blunting hyperoxic lung injury in this preclinical model may be relevant to the hundreds of thousands of patients who require treatment with high oxygen and who are at risk for developing severe pulmonary inflammation and consequent fibrosis. Strategies to disrupt CD40-CD40L interactions may offer a new mode of intervention for oxygen-induced acute respiratory distress syndrome and other inflammatory lung disorders.
Authors	A Adawi, Y Zhang, R Baggs, J Finkelstein, R P Phipps
Journal	The American journal of pathology (Am J Pathol) Vol. 152 Issue 3 Pg. 651-7 (Mar 1998) ISSN: 0002-9440 [Print] United States
PMID	9502405 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Antibodies, Monoclonal CD40 Antigens Ligands Membrane Glycoproteins CD40 Ligand Prostaglandin-Endoperoxide Synthases Oxygen
Topics	Animals Antibodies, Monoclonal (administration & dosage) CD40 Antigens (immunology, metabolism) CD40 Ligand Cricetinae Disease Models, Animal Humans Hyperoxia (chemically induced, enzymology, pathology, prevention & control) Immunohistochemistry Injections, Intraperitoneal Ligands Lung Diseases (chemically induced, enzymology, pathology, prevention & control) Male Membrane Glycoproteins (immunology, metabolism) Mice Mice, Inbred C57BL Oxygen Prostaglandin-Endoperoxide Synthases (metabolism)

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