Evidence that interleukin-6 does not play a role in the stimulation of
platelet production after induction of acute thrombocytopenia
RJ Hill, MK Warren, J Levin and J Gauldie
Department of Laboratory Medicine, University of California School of
Medicine, San Francisco.
The induction of thrombocytopenia results in elevated levels of
thrombopoietin (TPO), which can be detected in the plasma of experimental
animals. Acute, severe thrombocytopenia (platelet count less than 5% of
control) was produced in mice by the administration of either guinea pig or
rabbit antimouse platelet antiserum. Control mice received equal volumes of
normal serum. At various times after the induction of thrombocytopenia
(0.5, 1, 2, 3, 4, 6, 12, and 24 hours) citrated plasma was collected, and
circulating interleukin-6 (IL-6) levels were measured using the
IL-6-dependent murine hybridoma cell line B9. At no time points after
induction of thrombocytopenia were plasma IL-6 levels significantly
different from control animals that received normal serum. However,
injection of heterologous serum did result in slightly elevated plasma IL-6
levels (at 2 and 3 hours) compared with basal levels measured in uninjected
animals. This brief increase was not related to the production of
thrombocytopenia. Protein fractions from the plasma of thrombocytopenic
rabbits were also tested for the presence of IL-6. Preparations that
contained TPO, as shown by stimulation of megakaryocyte maturation in
vitro, did not contain detectable levels of IL-6. The ability of the B9
assay to detect the elevation of IL-6 levels in murine or rabbit plasma was
verified after the administration of bacterial endotoxin, which is known to
increase circulating IL-6 concentrations. IL-6 levels were highly elevated
in rabbit or mouse serum after the administration of 5 mg/kg or 1 mg/kg of
endotoxin, respectively. Anti-IL-6 antiserum did not neutralize the in
vitro megakaryocyte maturation activity of partially purified TPO from the
plasma of thrombocytopenic rabbits. In addition, IgG purified from the same
antiserum did not neutralize partially purified TPO, as shown after
incubation with TPO and subsequent precipitation with agarose- bound
protein A. These results show that, unlike TPO, levels of IL-6 do not
increase after the induction of acute, severe thrombocytopenia, and
strongly suggest that IL-6 does not mediate the thrombopoietic response to
acute thrombocytopenia. Although prolonged administration of IL-6 has been
shown to induce thrombocytosis, IL-6 and TPO are apparently different and
immunologically distinct molecules.
Volume 80,
Issue 2,
pp. 346-351,
07/15/1992
Copyright © 1992 by The American Society of Hematology
