Blood, 1 May 2003, Vol. 101, No. 9, pp. 3344-3345
Cracking chemokine paradigms: inhibition of idiopathic
pneumonia syndrome
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-1
in donor leukocytes, instead of decreasing IPS,
actually made it more aggressive. Deleting MIP-1 in the recipient
lungs but not donor leukocytes made no difference in the IPS course.
These investigators found that deletion of donor leukocyte MIP-1
resulted in decreased production of the anti-inflammatory
cytokine IL-13. Thus, contrary to the current paradigm, some chemokines
such as MIP-1 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.
Robert Hromas
University of New Mexico
