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Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3148-3151
Serum Levels of Substance P Are Elevated in Patients With Sickle Cell
Disease and Increase Further During Vaso-Occlusive Crisis
Lisa A. Michaels,
Kwaku Ohene-Frempong,
Huaqing Zhao, and
Steven
D. Douglas
From the Divisions of Hematology, Immunologic and Infectious
Diseases, and Biostatistics and Epidemiology, The Children's Hospital
of Philadelphia, the Department of Pediatrics, and Joseph Stokes Jr
Research Institute, University of Pennsylvania School of Medicine,
Philadelphia.
As a mediator of neurogenic inflammation and pain, we hypothesized
that levels of the neuropeptide Substance P (SP) would be elevated in
patients with sickle cell disease (SCD) with vaso-occlusive pain
crisis. SP is a known stimulator of tumor necrosis factor- (TNF-)
release and a promoter of interleukin-8 (IL-8), which are reported to
be increased in SCD. These cytokines enhance adhesion of leukocytes to
endothelium and may play a role in vaso-occlusive events. Serum levels
of IL-8, TNF, and SP were studied in three groups of children aged 2 to 18 years: 30 well children with SCD, 21 with SCD in pain crisis, and
20 healthy age-matched controls. Serum levels of SP were elevated in
all SCD patients and were highest in patients in pain crisis. The
percentage of sera with detectable levels of IL-8 (>5.0 pmol/L) was
increased in SCD patients as compared with the control group. IL-8
levels were similar for well SCD patients and those with pain. TNF
levels were not significantly different among the three groups. In
three children with SCD, SP was measured at baseline and again during
pain crisis. In each case, serum levels during pain crisis were higher
than they were when the patient was well. We conclude that levels of SP
are high in patients with SCD and increase during pain crisis. These
results imply that SP plays a prominent role in the pain and
inflammation of SCD and may be a measurable laboratory marker of
vaso-occlusive crisis. We speculate that neurokinin receptor
antagonists may have a therapeutic potential in the treatment of crisis
pain.
© 1998 by The American Society of Hematology.
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