Respiratory syncytial virus infection — Lung neutrophils during RSV infection

Adding IL-6 receptor blockade to methotrexate would improve ACR50 response in methotrexate-inadequate responders.

The overall arm missed its endpoint, though a seropositive subgroup showed a large and consistent effect.

Why it matched: shares IL6 · mechanism: Inflammation & innate immunity

MERTK in endothelial cells maintains barrier function and restrains neutrophil transendothelial migration, so deleting it specifically in endothelium should aggravate inflammatory lung injury.

Knocking MERTK down in primary human pulmonary microvascular endothelial cells increased neutrophil transmigration and dextran leak and disrupted adherens junctions and basal Rac1 activity, and global Mertk-null mice recruited more neutrophils and leaked more Evans blue during Pseudomonas aeruginosa pneumonia. But inducible endothelium-specific Mertk-null mice showed no difference from controls in either neutrophil migration into inflamed lungs or vascular permeability.

Why it matched: mechanism: Inflammation & innate immunity · failed the same way: Held in the model species, not beyond it

An oncolytic virus's inflammatory remodelling of the tumour microenvironment would recruit CAR T cells and improve their function in solid tumours.

Contrary to the hypothesis, VSV-mIFNβ infection caused attrition of murine EGFRvIII CAR T cells in a B16EGFRvIII model, despite producing a robust proinflammatory shift in the chemokine profile.

Why it matched: mechanism: Inflammation & innate immunity · failed the same way: Held in the model species, not beyond it

VCP, a complement inhibitor that protects nerve tissue in brain and spinal cord injury models, would protect the rat retina from light-induced degeneration.

In light-damaged retinas, VCP did not reduce photoreceptor loss, retinal stress or inflammation compared with saline. Injected VCP spread through the retina but was cleared within 1 to 3 hours.

Why it matched: mechanism: Inflammation & innate immunity · failed the same way: Held in the model species, not beyond it

Low-dose IL2 raises regulatory T cells, which reverse protein loss in the urine in animal models of nephrotic syndrome, so it would lower protein loss in children whose nephrotic syndrome resists all other drugs.

In 5 boys given six monthly cycles, IL2 raised regulatory T cells in some, but protein in the urine and kidney function did not change at any point. One child had an asthma attack after the first dose.

Why it matched: mechanism: Inflammation & innate immunity · failed the same way: Held in the model species, not beyond it