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LH Cox, T Downs, K Dagg, J Henthorn and SA Burstein
Department of Medicine, University of Oklahoma Health Sciences Center,
Oklahoma City.
Induction of experimental thrombocytopenia in rodents results in the
enhancement of megakaryocytic growth and differentiation. Interleukin-3
(IL-3) and IL-6, cytokines with a broad spectrum of biologic activities,
stimulate megakaryocytopoiesis in vitro. To determine if expression of
these factors might increase in response to experimental thrombocytopenia,
we measured steady-state levels of IL-3 and IL-6 mRNA following rabbit
antiplatelet serum (APS) injection. Groups of mice were injected
intravenously with 0.2 mL APS while control animals received rabbit
antilymphocyte serum (ALS), normal rabbit serum (NRS), or
phosphate-buffered saline (PBS). At various times up to 72 hours after
injection mice were exsanguinated and splenectomized. Platelet counts in
the experimental animals were less than 12% of controls. Splenic RNA was
hybridized in solution to 32P-UTP-labeled cRNA probes for IL-3 and IL-6.
RNase-resistant hybrids were resolved on denaturing gels and visualized
autoradiographically. IL-3 hybrids were undetectable at all time points
tested, irrespective of the film exposure time or specific activity of the
probe. Conversely, IL-6 hybrids were easily visualized and showed peak
expression at 1.5 to 2.0 hours. By 3 hours, IL-6 mRNA had returned almost
to the level of the controls. Similar results were observed in the bone
marrow, although maximal IL-6 mRNA in that tissue was observed 4 hours
following APS administration. To determine if this mRNA increment was
associated with a concomitant increase in bioactive protein, serum was
tested for its ability to stimulate IL-6-dependent B9 cells. At 1.75 hours
following injection, experimental animals showed a small but significant
increment in IL-6 activity compared with controls (200 +/- 30 U/mL IL-6
compared with 129 +/- 17 U/mL in ALS-injected controls, 106 +/- 17 U/mL in
NRS-injected controls and 84 +/- 17 U/mL in PBS-injected controls). The
data show that IL-6 mRNA and bioactive protein increase in response to
acute immunothrombocytopenia, while no increment in IL-3 is detectable.
These results suggest that IL-6 may play a role in the physiologic response
to acute immunothrombocytopenia.
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| Copyright © 1991 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||