Additive effects of infection and neutropenia on the induction of granulocytopoietic activity in vivo

Cancer. 1999 Jul 15;86(2):340-8.


Background: Granulocyte-colony stimulating factor (G-CSF) is a potent stimulator of granulocytopoiesis and granulocyte function. It has been used in the treatment of children with neutropenic infection; in this context, it was expected to shorten aplasia and limit the severity of infection. Clinical trials, however, have demonstrated conflicting results as to whether these aims can be met. Recently, the use of other, less lineage specific growth factors, such as interleukin (IL)-11 and stem cell factor (SCF), has also been discussed. The dynamics of growth factors and growth factor-regulating proteins during neutropenic infection, particularly in youngsters, are not well understood.

Methods: Serial blood samples from children and adolescents with infection during chemotherapy-induced neutropenia were assayed for C-reactive protein, white blood cell count, IL-11, SCF, G-CSF, IL-10, IL-4, IL-lalpha, and IL-1beta.

Results: Although no correlation could be demonstrated between endogenous IL-11 or SCF levels, infection, and leukocyte counts, endogenous G-CSF levels were increased during both aplasia and infection. However, only the additive effects of infection and neutropenia led to maximally stimulated endogenous G-CSF levels.

Conclusions: The elevated G-CSF levels in a majority of patients during severe neutropenic infection may explain why a therapeutic benefit of G-CSF treatment cannot be demonstrated in all cases. There remains, however, a subgroup of patients in whom infection and cytopenia do not yield a good G-CSF response. This latter group should be identified, because they might derive some benefit from adjuvant growth factor therapy. The authors predict that the efficacy of G-CSF in the treatment of patients with neutropenic fever might depend on each individual's ability to initiate the necessary cytokine production.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Antineoplastic Agents / adverse effects*
  • Child
  • Child, Preschool
  • Female
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Growth Substances / pharmacology*
  • Humans
  • Infant
  • Infections / immunology
  • Infections / physiopathology
  • Interleukin-11 / analysis
  • Interleukin-11 / pharmacology
  • Male
  • Neoplasms / drug therapy
  • Neutropenia / complications
  • Neutropenia / drug therapy
  • Neutropenia / physiopathology*
  • Patient Selection
  • Severity of Illness Index


  • Antineoplastic Agents
  • Growth Substances
  • Interleukin-11
  • Granulocyte Colony-Stimulating Factor