An allogeneic stem cell recipient is short of breath but otherwise is doing well. A chest X-ray finds extensive pulmonary infiltrates. Bronchoscopy reveals no infectious organisms. Stem cell transplantation physicians know the feeling of dread at what comes next. All too often, the patient dies on the ventilator within a few weeks from respiratory failure. This often- fatal clinical course has been termed idiopathic pneumonia syndrome (IPS). IPS has been discouraging to stem cell transplantation hematologists because it often strikes otherwise healthy patients and so little is known about its origin. IPS is a rapidly progressive infiltration of the recipient pulmonary parenchyma by donor T cells and monocytes. Similar to more classic graft-versus-host disease (GVHD), it occasionally responds to high-dose steroids.
Using a murine model of IPS, Panoskaltsis-Mortari and colleagues (page 3714) provided surprising insight into the pathogenesis of IPS. One would expect that chemokines, small proteins that are the major chemoattractants for leukocytes, would be responsible for the rapid influx of donor leukocytes into the lungs. But Panoskaltsis-Mortari et al found that deletion of the chemokine MIP-1α in donor leukocytes, instead of decreasing IPS, actually made it more aggressive. Deleting MIP-1α in the recipient lungs but not donor leukocytes made no difference in the IPS course. These investigators found that deletion of donor leukocyte MIP-1α resulted in decreased production of the anti-inflammatory cytokine IL-13. Thus, contrary to the current paradigm, some chemokines such as MIP-1α may actually down-regulate an inflammatory response by inducing other inhibitory cytokines. Perhaps an imbalance in chemokine production is at the heart of IPS. This also raises the intriguing possibility that in some situations patients with inflammatory diseases could actually benefit from treatment with chemokines.
