Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Induction of endogenous G-CSF production in neutropenia and infection - implications for post-infectious T-cell suppression

H Bönig MD 1, M Hannen MD 1, W Nürnberger MD 1, D Körholz MD 2, U Göbel MD 1

1 Heinrich-Heine University Center of Child Health, Dept Pediatric Hematology and Oncology, Düsseldorf, Germany, 2 University of Leipzig, Div Pediatric Hematology and Oncology, Leipzig, Germany,

AIMS: Granulocyte-colony stimulating factor (G-CSF) is a potent stimulator of granulocytopoiesis and granulocyte function. Recombinant G-CSF is used therapeutically to shorten chemotherapy-induced neutropenia. In most clinical studies it could thus reduce the overall incidence of neutropenic infection, but the number of very severe infections was not affected. In light of this, the dynamics of endogenous G-CSF and G-CSF regulating proteins need to be reconsidered. METHODS: Serial blood samples from patients with infections during chemotherapy-induced neutropenia were collected and investigated. G-CSF and interleukins (IL-) were measured by ELISA, CRP and WBC by routine laboratory tests. RESULTS: Endogenous G-CSF levels were increased 2.7-fold during aplasia, and 3-fold during infection. However, only the additive effects of infection and neutropenia lead to maximally stimulated G-CSF levels, which were >75-fold higher in comparison to non-neutropenic patients without infections. A correlation of G-CSF levels with levels of endogenous IL-1, IL-4 and IL-10, which we had previously identified as regulators of G-CSF production in vitro, could not be demonstrated. CONCLUSIONS: During neutropenic infection, "therapeutic" G-CSF plasma levels are often achieved. Some poor producers of endogenous G-CSF, however, may benefit from G-CSF injections. A relevant side-effect or G-CSF - both endogenous and recombinant - is its prolonged suppression of IL-12. Since neutropenic infections induce significant amounts of G-CSF, they can impair T-cell function, and thus aggravate the infection. The data argue for a stringent anti-infectious prophylaxis and a very early detection and treatment of an impending infection.

KEY WORDS: neutropenia, infection, immune suppression.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on immunosurveillance.